A. Bartke - Academia.edu (original) (raw)

Papers by A. Bartke

Research paper thumbnail of Regulation of testicular LH/hCG receptors in golden hamsters (Mesocricetus auratus) during development

Reproduction, 1985

During prepubertal development in the golden hamster, there are major age-related changes in the ... more During prepubertal development in the golden hamster, there are major age-related changes in the number of testicular LH/hCG receptors. Between 22 and 35 days of age, there was > 10-fold increase in testicular LH/hCG receptors, followed by a decrease at Day 37. Concomitant with, but preceding slightly, the changes in receptors, were increases in plasma LH and FSH and most noticeably prolactin concentrations, between Days 10 and 20 of age. Inhibition of the increases in plasma levels of prolactin by daily injections of bromocriptine, between 14 and 31 days of age, resulted in suppressed testicular and seminal vesicle weights, and decreased content and concentration of testicular LH/hCG receptors. Similarly, the premature increase in plasma prolactin concentrations in prepubertal hamsters between 6 and 20 days of age, by means of ectopic pituitary transplants, resulted in increased testicular and seminal vesicle weights, as well as an increase in the concentration of testicular LH/hCG receptors. These results strongly suggest that increases in plasma prolactin values during development are important in enhancement of the development of testicular LH/hCG receptors.

Research paper thumbnail of Body size, GH signaling and longevity

Experimental Gerontology, 2013

concentration. HsCRP concentrations increased as the values of BMI, the amount of adipose tissue,... more concentration. HsCRP concentrations increased as the values of BMI, the amount of adipose tissue, waist circumference, insulin concentration and HOMA index increased. The value of BMI, insulin concentration and WHR index had the greatest impact on hsCRP concentration. The results of the study may suggest a proinflammatory role of leptin and a positive effect of a low calorie diet on decreasing the inflammatory process. Observed inversely proportional relationship between adiponectin concentration and inflammatory cytokines levels may confirm anti-inflammatory effect of this adipokine. Decrease in adiponectin concentration, which is proportional to the degree of insulin resistance and obesity, may be one of the factors leading to the development of a proinflammatory state in persons with obesity. Low adiponectin concentration in obese persons is a predictor for metabolic syndrome.

Research paper thumbnail of Down regulation of masked and unmasked insulin receptors in the liver of transgenic mice expressing bovine growth hormone gene

Research paper thumbnail of Neuroendocrine changes in male hamsters following photostimulation

Journal of Experimental Zoology, 1984

Transfer of gonadally regressed male golden hamsters from a short (5 L:19 D) to a stimulatory (14... more Transfer of gonadally regressed male golden hamsters from a short (5 L:19 D) to a stimulatory (14 L:10 D) photoperiod elicits, within 24 hr, significant changes in hypothalamic dopamine, serotonin, and possibly norepinephrine metabolism. Hypothalamic LHRH content was significantly elevated in short-photoperiod animals, but within 24 hr of transfer to a 14:10 photoperiod, LHRH declined to levels not different from those in hamsters maintained continuously in a long photoperiod. Plasma FSH levels were also

Research paper thumbnail of Luteolytic effect of azastene in the nonhuman primate

Obstetrics and gynecology, 1982

The ability to block steroidogenesis with 4,4,17-alpha-trimethylandrost-5-eno[2,3,-d]isoxazol-17-... more The ability to block steroidogenesis with 4,4,17-alpha-trimethylandrost-5-eno[2,3,-d]isoxazol-17-ol (azastene) was studied in 3 different models. Oral administration of 500 mg to rhesus monkeys on different days of their luteal phase induced marked depression of circulating progesterone concentrations, and in some cases early onset of menses. Simultaneous administration of human chorionic gonadotropin (hCG) during the midluteal phase did not overcome the luteolytic effect of azastene. Concentrations of 50 micrograms/ml of azastene inhibited testosterone secretion by decapsulated mice testes in vitro in response to hCG [controls, 1165 +/- 196 ng/ml, azastene, 306 +/- 40 ng/ml (P less than .01)]. Production of progesterone by dispersed luteal cells from rhesus monkey corpora lutea was markedly inhibited by the presence of 25 and 50 micrograms/ml azastene in the incubation media (P less than .05 and less than .01, respectively). The availability of a compound that blocks in vivo and in...

Research paper thumbnail of Effects of human growth hormone on reproductive and neuroendocrine functions in transgenic mice

Biotechnology (Reading, Mass.), 1991

1. Biotechnology. 1991;16:237-48. Effects of human growth hormone on reproductive and neuroendocr... more 1. Biotechnology. 1991;16:237-48. Effects of human growth hormone on reproductive and neuroendocrine functions in transgenic mice. Bartke A, Shire JG, Chandrashekar V, Steger RW, Mayerhofer A, Amador AG, Bain P, Tang K, Yun JS, Wagner TE. ...

Research paper thumbnail of Relationship of the length of exposure to short photoperiod to the effect of prolactin on pituitary and testicular function in the golden hamster

Reproduction, 1983

Adult male golden hamsters were given ectopic pituitary transplants at the time of transfer from ... more Adult male golden hamsters were given ectopic pituitary transplants at the time of transfer from a long (stimulatory) photoperiod (14 h L:10 h D) to a short photoperiod (5L:19D) or at various intervals thereafter. Grafts given at the time of transfer to 5L:19D failed to maintain plasma FSH levels significantly above those observed in sham-operated controls or to prevent regression of the testes. Grafts given after 4 weeks in 5L :19D increased plasma FSH levels and significantly diminished the decrease in testicular volume. Grafts given 14 weeks after transfer to 5L :19D caused a modest increase in plasma FSH levels and did not significantly alter the time course of testicular redevelopment. Similarly, grafts given 18 weeks after transfer to 5L :19D had no effect on testicular weight measured 2\m=.\5weeks later. These results indicate that the ability of prolactin (secreted by the grafted pituitary) to increase testicular size and the responsiveness of the hypothalamic\p=n-\pituitarysystem to prolactin gradually increase during short photoperiod-induced testicular regression, are maximal when the testes are fully regressed and decrease again during spontaneous redevelopment of the testes. We suggest that the effects of prolactin on the testes in golden hamsters are partly mediated by prolactin-induced stimulation of FSH release from the in-situ pituitary.

Research paper thumbnail of Effects of expression of human or bovine growth hormone genes on sperm production and male reproductive performance in four lines of transgenic mice

Reproduction, 1992

OH 45701, USA Summary. Reproductive performance was studied in transgenic males from lines expres... more OH 45701, USA Summary. Reproductive performance was studied in transgenic males from lines expressing and transmitting four hybrid genes: mouse metallothionein-I/human growth hormone (GH) (MT/hGH), MT/hGH placental variant (MT/hGH\m=.\V),MT/bovine GH (MT/bGH) and phosphoenolpyruvate carboxykinase/bGH (PEPCK/bGH). Each male was exposed to three normal females for 1 week and to three different normal females for another week. Females were examined for vaginal plugs and necropsied on day 14 of pregnancy. Males were killed for analysis of organ weights, numbers of testicular spermatids, numbers of epididymal sperm and measurements of plasma glucose concentration. Fertility of MT/hGH and MT/hGH\m=.\V transgenic males was significantly lower than in normal males, primarily because most males failed to impregnate any females. In females that became pregnant, the numbers of corpora lutea, total fetuses and live fetuses did not differ from those in females mated to normal (nontransgenic) males. Fetal crown\p=n-\rumplength on day 14 of pregnancy did not differ between litters sired by normal or by transgenic males. Weights of testes and seminal vesicles were significantly greater in all four types of transgenic male, but daily sperm production per unit weight (g\p=n-\1) of testis was not affected and epididymal sperm reserves were either normal or slightly higher than normal. Plasma glucose concentrations were significantly higher in PEPCK/bGH mice than in other mice. Average or individual reproductive performance of transgenic males from the various lines did not correlate with any of the parameters examined except for significantly heavier seminal vesicles in MT/hGH and MT/hGH\m=.\V males than in normal males; these transgenic males exhibited a high incidence of infertility. Since hGH and hGH\m=.\V, but not bGH, are lactogenic in rodents, it was concluded that chronic stimulation of GH and prolactin receptors by ectopically produced human GHs in transgenic mice compromises male fertility by an unknown mechanism. Reduced fertility of transgenic males with MT/hGH or MT/hGH\m=.\V hybrid genes is due to failure to inseminate or impregnate females rather than to reduced numbers of spermatozoa or gross changes in the male reproductive system.

Research paper thumbnail of Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure

Pharmacology Biochemistry and Behavior, 1984

exposure to Ag-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to... more exposure to Ag-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidio| (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20/,g T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

Research paper thumbnail of Neonatal exposure to DES in BALB/c male mice: Effects on pituitary-gonadal function

Pharmacology Biochemistry and Behavior, 1985

mice were injected with diethylstilbestrol (DES), estradiol benzoate (E~B), testosterone propiona... more mice were injected with diethylstilbestrol (DES), estradiol benzoate (E~B), testosterone propionate (TP), progesterone or DES, in combination with E2B, TP or progesterone and examined in adulthood. Body weight was reduced in males exposed to DES, TP or DES + TP, while testicular weight was reduced in animals injected with DES, E2B, TP, DES + TP or DES + progesterone. Exposure to DES and/or E~B also produced reproductive tract abnormalities and concomitant progesterone exposure did not further affect this parameter. Concomitant DES did not further alter the reduced plasma luteinizing hormone (LH) levels attributable to neonatal TP or E~B treatment. Plasma follicle-stimulating hormone (FSH) levels in intact males were increased by DES, DES + progesterone or progesterone alone. Assessment of the feedback effects of exogenous gonadal steroids on pituitary gonadotropin release in castrated adults indicated that injection of 125 p,g TP further increased the already elevated post-castration levels of LH and FSI-I in mice neouatally exposed to progesterone. The increase in testosterone (T) concentration after intratesticular human chorionic gonadotropin (hCG) administration was significantly attenuated in mice neouatally exposed to DES plus E~B or to progesterone. Basal testicular

Research paper thumbnail of Effects of delta-9-tetrahydrocannabinol exposure on adrenal medullary function: Evidence of an acute effect and development of tolerance in chronic treatments

Pharmacology Biochemistry and Behavior, 1991

Previous studies have shown that the secretion of several stress-related hormones can be altered ... more Previous studies have shown that the secretion of several stress-related hormones can be altered by exposure to marihuana or its purified constituents. The purpose of this study was to examine changes in adrenal medullary function caused by acute, subchronic and chronic treatments with two different doses of delta-9-tetrahydrocannabinol (THC). Acute exposure to THC caused a significant decrease in the adrenal medulla contents of both norepinephrine (NE) and epinephrine (E) and a significant increase in the E/NE ratio. These effects were mainly observed with the highest dose of THC, but they were not accompanied by a statistically significant decrease in adrenal medulla tyrosine hydroxylase activity, the rate-limiting enzyme in the catecholamine (CA) synthesis. These effects disappeared after seven or fourteen days of a daily THC treatment, which suggests the development of tolerance to this drug. Analysis of plasma PRL, ACTH and corticosterone levels showed some THC-related changes in these hormones. THC-induced modifications in ACTH and corticosterone were not in parallel to the changes in the adrenal medulla function, whereas those effects of acute THC on PRL release were statistically correlated with decreases of CA contents following acute THC. In conclusion, acute exposure to THC caused an alteration in the adrenal medullary function, reflected by a fall in endogenous stores of both CAs which could influence the adrenal medullary response to stress situations. This acute effect of THC could be mediated by the pituitary secretion of PRL, although the possibility of an effect directly exerted on the adrenal medulla chromaffin cells should be also considered. This acute effect disappeared after prolonged treatments, suggesting the development of tolerance to this drug. Cannabinoids Delta-9-tetrahydrocannabinol Adrenal medulla Catecholamine Tyrosine hydroxylase

Research paper thumbnail of What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Mechanisms of Ageing and Development, 2005

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longev... more Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems-although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.

Research paper thumbnail of Neuroendocrine and Pharmacological Manipulations to Assess How Caloric Restriction Increases Life Span

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2001

Research paper thumbnail of Concentration of free growth hormone-binding protein in the serum of mice is not regulated by growth hormone

Journal of Endocrinology, 1997

Ames dwarf mice that do not express growth hormone (GH) or prolactin (PRL) genes were used to stu... more Ames dwarf mice that do not express growth hormone (GH) or prolactin (PRL) genes were used to study the effects of GH deficiency on the presence and the characteristics of GH-binding protein (GHBP) in serum. Chromatographic techniques were used to allow characterization of biological rather than immunological activity of GHBP. Two GH-binding fractions were found in dwarf mice serum, one with low affinity and high capacity (GHBPI) and one with high affinity, low capacity and lower molecular mass (GHBPII). Serum concentration of the high-affinity GHBP was 0·73 ± 0·03 nm with a Kd of 6·3 ± 1·7 nm. Since Ames dwarf mice have no GH in the circulation, all the GHBP is free. Interestingly, the concentration of GHBP in dwarf mice was similar to the levels of free GHBP measured in normal mice from the same line. Moreover, this value (0·7 nm) closely resembles the concentration of free GHBP in the serum of transgenic mice overexpressing GH, in which peripheral GH levels are grossly elevated. ...

Research paper thumbnail of Influence of Prolactin on Male Fertility in Dwarf Mice

Journal of Endocrinology, 1966

Research paper thumbnail of Possible role of dopamine and noradrenaline in the regulation of prolactin secretion from an ectopic anterior pituitary gland in female rats

Journal of Endocrinology, 1987

It was recently reported that anterior pituitary tissue transplanted to an ectopic site contains ... more It was recently reported that anterior pituitary tissue transplanted to an ectopic site contains measurable amounts of dopamine and noradrenaline. To examine the possibility of local catecholaminergic control of prolactin secretion from ectopic pituitaries, pituitary grafted and sham-operated female rats were submitted to several pharmacological treatments modifying catecholamine synthesis. Administration of a single dose of α-methyl-p-tyrosine (α-MPT) significantly reduced dopamine content in the graft, while noradrenaline content was not modified. Similar changes in the contents of dopamine and noradrenaline after α-MPT administration were observed in the hypothalamus and in the in-situ pituitary in both grafted and sham-operated rats. Plasma concentrations of prolactin were increased in both grafted and sham-operated rats after administration of α-MPT. A single injection of l-3,4-dihydroxyphenylalanine (l-DOPA) increased dopamine content in the ectopic pituitary gland without alt...

Research paper thumbnail of Concentration of Gonadotrophins in the Plasma and Testicular Responsiveness to Gonadotrophic Stimulation in Androgen-Deficient C57BL/10J Mice

Journal of Endocrinology, 1977

Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, U.S.A. (Received ... more Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, U.S.A. (Received 24 May 1977) Deficient testicular function was suspected in male C57BL/10J mice from the observations that they have small testes (Shire & Bartke, 1972) and fail to produce the androgen-dependent pregnancy-blocking pheromone (Chapman & Whitten, 1969). Comparison with male DBA/2J mice and several other strains indicated that C57BL/10J mice have fewer spermatogonia, spermatocytes and spermatids, low testicular weight, a progressive decrease in the absolute weight of the testes after sexual maturation, excessive accumulation of esterified cholesterol in the testes and a low level of testosterone in the plasma (Bartke & Shire, 1972; Shire & Bartke, 1972; Bartke, 1974). The relative androgen deficiency of the C57BL/10J mice is also suggested by the observations of Ivanyi (1973), Hill, Clemens, Liu, Vessel & Johnson (1975) and Hoppe (1975). To define the causes of androgen deficiency in C57BL/...

Research paper thumbnail of Testicular Function in Strains of Mice Selected for Differences in Gonadotrophin-Induced Ovulation Rate

Journal of Endocrinology, 1981

Mice were selected on the basis of ovulatory responses to injections of pregnant mare serum gonad... more Mice were selected on the basis of ovulatory responses to injections of pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG). Various parameters of pituitary and gonadal function as well as responsiveness to exogenous gonadotrophins were examined in males from high induced-ovulation rate (HIOV) and low induced-ovulation rate (LIOV) lines. Testicular weight, seminal vesicle weight and plasma LH levels were lower in HIOV than in LIOV males, while plasma concentrations of FSH and testosterone did not differ. Binding of FSH, but not of LH, in the testes was significantly higher in HIOV mice. Twenty-four hours after administration of hCG, plasma testosterone levels were higher and testicular LH binding sites appeared more depleted in HIOV than in LIOV males. Production of testosterone by decapsulated testes in vitro was significantly higher in HIOV than in LIOV mice under basal conditions, as well as in the presence of LH, FSH, hCG or PMSG. It was concluded th...

Research paper thumbnail of Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

Journal of Endocrinology, 2012

Adiponectin is positively correlated with longevity and negatively correlated with many obesity-r... more Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our res...

Research paper thumbnail of Growth Hormone (GH) Binding and Effects of GH Analogs in Transgenic Mice

Experimental Biology and Medicine, 1994

... o,t RICHARD W. STEGER,” ANDRZEJ BARTKE,”” DANIEL TURYN , ~ CLAUDIO C. AGUILAR,~ ANA I. SOTE D... more ... o,t RICHARD W. STEGER,” ANDRZEJ BARTKE,”” DANIEL TURYN , ~ CLAUDIO C. AGUILAR,~ ANA I. SOTE Department of Physiology, * Southern Illinois University, Carbondale, Illinois 62901; XIAO Z. CHEN,$ AND JOHN J. KOPCHICKS ... 27. Baxter RC, Zaltsman Z, Turtle JR. ...

Research paper thumbnail of Regulation of testicular LH/hCG receptors in golden hamsters (Mesocricetus auratus) during development

Reproduction, 1985

During prepubertal development in the golden hamster, there are major age-related changes in the ... more During prepubertal development in the golden hamster, there are major age-related changes in the number of testicular LH/hCG receptors. Between 22 and 35 days of age, there was > 10-fold increase in testicular LH/hCG receptors, followed by a decrease at Day 37. Concomitant with, but preceding slightly, the changes in receptors, were increases in plasma LH and FSH and most noticeably prolactin concentrations, between Days 10 and 20 of age. Inhibition of the increases in plasma levels of prolactin by daily injections of bromocriptine, between 14 and 31 days of age, resulted in suppressed testicular and seminal vesicle weights, and decreased content and concentration of testicular LH/hCG receptors. Similarly, the premature increase in plasma prolactin concentrations in prepubertal hamsters between 6 and 20 days of age, by means of ectopic pituitary transplants, resulted in increased testicular and seminal vesicle weights, as well as an increase in the concentration of testicular LH/hCG receptors. These results strongly suggest that increases in plasma prolactin values during development are important in enhancement of the development of testicular LH/hCG receptors.

Research paper thumbnail of Body size, GH signaling and longevity

Experimental Gerontology, 2013

concentration. HsCRP concentrations increased as the values of BMI, the amount of adipose tissue,... more concentration. HsCRP concentrations increased as the values of BMI, the amount of adipose tissue, waist circumference, insulin concentration and HOMA index increased. The value of BMI, insulin concentration and WHR index had the greatest impact on hsCRP concentration. The results of the study may suggest a proinflammatory role of leptin and a positive effect of a low calorie diet on decreasing the inflammatory process. Observed inversely proportional relationship between adiponectin concentration and inflammatory cytokines levels may confirm anti-inflammatory effect of this adipokine. Decrease in adiponectin concentration, which is proportional to the degree of insulin resistance and obesity, may be one of the factors leading to the development of a proinflammatory state in persons with obesity. Low adiponectin concentration in obese persons is a predictor for metabolic syndrome.

Research paper thumbnail of Down regulation of masked and unmasked insulin receptors in the liver of transgenic mice expressing bovine growth hormone gene

Research paper thumbnail of Neuroendocrine changes in male hamsters following photostimulation

Journal of Experimental Zoology, 1984

Transfer of gonadally regressed male golden hamsters from a short (5 L:19 D) to a stimulatory (14... more Transfer of gonadally regressed male golden hamsters from a short (5 L:19 D) to a stimulatory (14 L:10 D) photoperiod elicits, within 24 hr, significant changes in hypothalamic dopamine, serotonin, and possibly norepinephrine metabolism. Hypothalamic LHRH content was significantly elevated in short-photoperiod animals, but within 24 hr of transfer to a 14:10 photoperiod, LHRH declined to levels not different from those in hamsters maintained continuously in a long photoperiod. Plasma FSH levels were also

Research paper thumbnail of Luteolytic effect of azastene in the nonhuman primate

Obstetrics and gynecology, 1982

The ability to block steroidogenesis with 4,4,17-alpha-trimethylandrost-5-eno[2,3,-d]isoxazol-17-... more The ability to block steroidogenesis with 4,4,17-alpha-trimethylandrost-5-eno[2,3,-d]isoxazol-17-ol (azastene) was studied in 3 different models. Oral administration of 500 mg to rhesus monkeys on different days of their luteal phase induced marked depression of circulating progesterone concentrations, and in some cases early onset of menses. Simultaneous administration of human chorionic gonadotropin (hCG) during the midluteal phase did not overcome the luteolytic effect of azastene. Concentrations of 50 micrograms/ml of azastene inhibited testosterone secretion by decapsulated mice testes in vitro in response to hCG [controls, 1165 +/- 196 ng/ml, azastene, 306 +/- 40 ng/ml (P less than .01)]. Production of progesterone by dispersed luteal cells from rhesus monkey corpora lutea was markedly inhibited by the presence of 25 and 50 micrograms/ml azastene in the incubation media (P less than .05 and less than .01, respectively). The availability of a compound that blocks in vivo and in...

Research paper thumbnail of Effects of human growth hormone on reproductive and neuroendocrine functions in transgenic mice

Biotechnology (Reading, Mass.), 1991

1. Biotechnology. 1991;16:237-48. Effects of human growth hormone on reproductive and neuroendocr... more 1. Biotechnology. 1991;16:237-48. Effects of human growth hormone on reproductive and neuroendocrine functions in transgenic mice. Bartke A, Shire JG, Chandrashekar V, Steger RW, Mayerhofer A, Amador AG, Bain P, Tang K, Yun JS, Wagner TE. ...

Research paper thumbnail of Relationship of the length of exposure to short photoperiod to the effect of prolactin on pituitary and testicular function in the golden hamster

Reproduction, 1983

Adult male golden hamsters were given ectopic pituitary transplants at the time of transfer from ... more Adult male golden hamsters were given ectopic pituitary transplants at the time of transfer from a long (stimulatory) photoperiod (14 h L:10 h D) to a short photoperiod (5L:19D) or at various intervals thereafter. Grafts given at the time of transfer to 5L:19D failed to maintain plasma FSH levels significantly above those observed in sham-operated controls or to prevent regression of the testes. Grafts given after 4 weeks in 5L :19D increased plasma FSH levels and significantly diminished the decrease in testicular volume. Grafts given 14 weeks after transfer to 5L :19D caused a modest increase in plasma FSH levels and did not significantly alter the time course of testicular redevelopment. Similarly, grafts given 18 weeks after transfer to 5L :19D had no effect on testicular weight measured 2\m=.\5weeks later. These results indicate that the ability of prolactin (secreted by the grafted pituitary) to increase testicular size and the responsiveness of the hypothalamic\p=n-\pituitarysystem to prolactin gradually increase during short photoperiod-induced testicular regression, are maximal when the testes are fully regressed and decrease again during spontaneous redevelopment of the testes. We suggest that the effects of prolactin on the testes in golden hamsters are partly mediated by prolactin-induced stimulation of FSH release from the in-situ pituitary.

Research paper thumbnail of Effects of expression of human or bovine growth hormone genes on sperm production and male reproductive performance in four lines of transgenic mice

Reproduction, 1992

OH 45701, USA Summary. Reproductive performance was studied in transgenic males from lines expres... more OH 45701, USA Summary. Reproductive performance was studied in transgenic males from lines expressing and transmitting four hybrid genes: mouse metallothionein-I/human growth hormone (GH) (MT/hGH), MT/hGH placental variant (MT/hGH\m=.\V),MT/bovine GH (MT/bGH) and phosphoenolpyruvate carboxykinase/bGH (PEPCK/bGH). Each male was exposed to three normal females for 1 week and to three different normal females for another week. Females were examined for vaginal plugs and necropsied on day 14 of pregnancy. Males were killed for analysis of organ weights, numbers of testicular spermatids, numbers of epididymal sperm and measurements of plasma glucose concentration. Fertility of MT/hGH and MT/hGH\m=.\V transgenic males was significantly lower than in normal males, primarily because most males failed to impregnate any females. In females that became pregnant, the numbers of corpora lutea, total fetuses and live fetuses did not differ from those in females mated to normal (nontransgenic) males. Fetal crown\p=n-\rumplength on day 14 of pregnancy did not differ between litters sired by normal or by transgenic males. Weights of testes and seminal vesicles were significantly greater in all four types of transgenic male, but daily sperm production per unit weight (g\p=n-\1) of testis was not affected and epididymal sperm reserves were either normal or slightly higher than normal. Plasma glucose concentrations were significantly higher in PEPCK/bGH mice than in other mice. Average or individual reproductive performance of transgenic males from the various lines did not correlate with any of the parameters examined except for significantly heavier seminal vesicles in MT/hGH and MT/hGH\m=.\V males than in normal males; these transgenic males exhibited a high incidence of infertility. Since hGH and hGH\m=.\V, but not bGH, are lactogenic in rodents, it was concluded that chronic stimulation of GH and prolactin receptors by ectopically produced human GHs in transgenic mice compromises male fertility by an unknown mechanism. Reduced fertility of transgenic males with MT/hGH or MT/hGH\m=.\V hybrid genes is due to failure to inseminate or impregnate females rather than to reduced numbers of spermatozoa or gross changes in the male reproductive system.

Research paper thumbnail of Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure

Pharmacology Biochemistry and Behavior, 1984

exposure to Ag-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to... more exposure to Ag-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidio| (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20/,g T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

Research paper thumbnail of Neonatal exposure to DES in BALB/c male mice: Effects on pituitary-gonadal function

Pharmacology Biochemistry and Behavior, 1985

mice were injected with diethylstilbestrol (DES), estradiol benzoate (E~B), testosterone propiona... more mice were injected with diethylstilbestrol (DES), estradiol benzoate (E~B), testosterone propionate (TP), progesterone or DES, in combination with E2B, TP or progesterone and examined in adulthood. Body weight was reduced in males exposed to DES, TP or DES + TP, while testicular weight was reduced in animals injected with DES, E2B, TP, DES + TP or DES + progesterone. Exposure to DES and/or E~B also produced reproductive tract abnormalities and concomitant progesterone exposure did not further affect this parameter. Concomitant DES did not further alter the reduced plasma luteinizing hormone (LH) levels attributable to neonatal TP or E~B treatment. Plasma follicle-stimulating hormone (FSH) levels in intact males were increased by DES, DES + progesterone or progesterone alone. Assessment of the feedback effects of exogenous gonadal steroids on pituitary gonadotropin release in castrated adults indicated that injection of 125 p,g TP further increased the already elevated post-castration levels of LH and FSI-I in mice neouatally exposed to progesterone. The increase in testosterone (T) concentration after intratesticular human chorionic gonadotropin (hCG) administration was significantly attenuated in mice neouatally exposed to DES plus E~B or to progesterone. Basal testicular

Research paper thumbnail of Effects of delta-9-tetrahydrocannabinol exposure on adrenal medullary function: Evidence of an acute effect and development of tolerance in chronic treatments

Pharmacology Biochemistry and Behavior, 1991

Previous studies have shown that the secretion of several stress-related hormones can be altered ... more Previous studies have shown that the secretion of several stress-related hormones can be altered by exposure to marihuana or its purified constituents. The purpose of this study was to examine changes in adrenal medullary function caused by acute, subchronic and chronic treatments with two different doses of delta-9-tetrahydrocannabinol (THC). Acute exposure to THC caused a significant decrease in the adrenal medulla contents of both norepinephrine (NE) and epinephrine (E) and a significant increase in the E/NE ratio. These effects were mainly observed with the highest dose of THC, but they were not accompanied by a statistically significant decrease in adrenal medulla tyrosine hydroxylase activity, the rate-limiting enzyme in the catecholamine (CA) synthesis. These effects disappeared after seven or fourteen days of a daily THC treatment, which suggests the development of tolerance to this drug. Analysis of plasma PRL, ACTH and corticosterone levels showed some THC-related changes in these hormones. THC-induced modifications in ACTH and corticosterone were not in parallel to the changes in the adrenal medulla function, whereas those effects of acute THC on PRL release were statistically correlated with decreases of CA contents following acute THC. In conclusion, acute exposure to THC caused an alteration in the adrenal medullary function, reflected by a fall in endogenous stores of both CAs which could influence the adrenal medullary response to stress situations. This acute effect of THC could be mediated by the pituitary secretion of PRL, although the possibility of an effect directly exerted on the adrenal medulla chromaffin cells should be also considered. This acute effect disappeared after prolonged treatments, suggesting the development of tolerance to this drug. Cannabinoids Delta-9-tetrahydrocannabinol Adrenal medulla Catecholamine Tyrosine hydroxylase

Research paper thumbnail of What evidence is there for the existence of individual genes with antagonistic pleiotropic effects?

Mechanisms of Ageing and Development, 2005

Classical evolutionary theory predicts the existence of genes with antagonistic effects on longev... more Classical evolutionary theory predicts the existence of genes with antagonistic effects on longevity and various components of early-life fitness. Quantitative genetic studies have provided convincing evidence that such genes exist. However, antagonistic pleiotropic effects have rarely been attributed to individual loci. We examine several classes of longevity-assurance genes: those involved in regulation of the gonad; the insulin-like growth factor pathway; free-radical scavenging; heat shock proteins and apoptosis. We find initial evidence that antagonistic pleiotropic effects are pervasive in each of these classes of genes and in various model systems-although most studies lack explicit studies of fitness components. This is particularly true of human studies. Very little is known about the early-life fitness effects of longevity loci. Given the possible medical importance of such effects we urge their future study.

Research paper thumbnail of Neuroendocrine and Pharmacological Manipulations to Assess How Caloric Restriction Increases Life Span

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2001

Research paper thumbnail of Concentration of free growth hormone-binding protein in the serum of mice is not regulated by growth hormone

Journal of Endocrinology, 1997

Ames dwarf mice that do not express growth hormone (GH) or prolactin (PRL) genes were used to stu... more Ames dwarf mice that do not express growth hormone (GH) or prolactin (PRL) genes were used to study the effects of GH deficiency on the presence and the characteristics of GH-binding protein (GHBP) in serum. Chromatographic techniques were used to allow characterization of biological rather than immunological activity of GHBP. Two GH-binding fractions were found in dwarf mice serum, one with low affinity and high capacity (GHBPI) and one with high affinity, low capacity and lower molecular mass (GHBPII). Serum concentration of the high-affinity GHBP was 0·73 ± 0·03 nm with a Kd of 6·3 ± 1·7 nm. Since Ames dwarf mice have no GH in the circulation, all the GHBP is free. Interestingly, the concentration of GHBP in dwarf mice was similar to the levels of free GHBP measured in normal mice from the same line. Moreover, this value (0·7 nm) closely resembles the concentration of free GHBP in the serum of transgenic mice overexpressing GH, in which peripheral GH levels are grossly elevated. ...

Research paper thumbnail of Influence of Prolactin on Male Fertility in Dwarf Mice

Journal of Endocrinology, 1966

Research paper thumbnail of Possible role of dopamine and noradrenaline in the regulation of prolactin secretion from an ectopic anterior pituitary gland in female rats

Journal of Endocrinology, 1987

It was recently reported that anterior pituitary tissue transplanted to an ectopic site contains ... more It was recently reported that anterior pituitary tissue transplanted to an ectopic site contains measurable amounts of dopamine and noradrenaline. To examine the possibility of local catecholaminergic control of prolactin secretion from ectopic pituitaries, pituitary grafted and sham-operated female rats were submitted to several pharmacological treatments modifying catecholamine synthesis. Administration of a single dose of α-methyl-p-tyrosine (α-MPT) significantly reduced dopamine content in the graft, while noradrenaline content was not modified. Similar changes in the contents of dopamine and noradrenaline after α-MPT administration were observed in the hypothalamus and in the in-situ pituitary in both grafted and sham-operated rats. Plasma concentrations of prolactin were increased in both grafted and sham-operated rats after administration of α-MPT. A single injection of l-3,4-dihydroxyphenylalanine (l-DOPA) increased dopamine content in the ectopic pituitary gland without alt...

Research paper thumbnail of Concentration of Gonadotrophins in the Plasma and Testicular Responsiveness to Gonadotrophic Stimulation in Androgen-Deficient C57BL/10J Mice

Journal of Endocrinology, 1977

Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, U.S.A. (Received ... more Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts 01545, U.S.A. (Received 24 May 1977) Deficient testicular function was suspected in male C57BL/10J mice from the observations that they have small testes (Shire & Bartke, 1972) and fail to produce the androgen-dependent pregnancy-blocking pheromone (Chapman & Whitten, 1969). Comparison with male DBA/2J mice and several other strains indicated that C57BL/10J mice have fewer spermatogonia, spermatocytes and spermatids, low testicular weight, a progressive decrease in the absolute weight of the testes after sexual maturation, excessive accumulation of esterified cholesterol in the testes and a low level of testosterone in the plasma (Bartke & Shire, 1972; Shire & Bartke, 1972; Bartke, 1974). The relative androgen deficiency of the C57BL/10J mice is also suggested by the observations of Ivanyi (1973), Hill, Clemens, Liu, Vessel & Johnson (1975) and Hoppe (1975). To define the causes of androgen deficiency in C57BL/...

Research paper thumbnail of Testicular Function in Strains of Mice Selected for Differences in Gonadotrophin-Induced Ovulation Rate

Journal of Endocrinology, 1981

Mice were selected on the basis of ovulatory responses to injections of pregnant mare serum gonad... more Mice were selected on the basis of ovulatory responses to injections of pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG). Various parameters of pituitary and gonadal function as well as responsiveness to exogenous gonadotrophins were examined in males from high induced-ovulation rate (HIOV) and low induced-ovulation rate (LIOV) lines. Testicular weight, seminal vesicle weight and plasma LH levels were lower in HIOV than in LIOV males, while plasma concentrations of FSH and testosterone did not differ. Binding of FSH, but not of LH, in the testes was significantly higher in HIOV mice. Twenty-four hours after administration of hCG, plasma testosterone levels were higher and testicular LH binding sites appeared more depleted in HIOV than in LIOV males. Production of testosterone by decapsulated testes in vitro was significantly higher in HIOV than in LIOV mice under basal conditions, as well as in the presence of LH, FSH, hCG or PMSG. It was concluded th...

Research paper thumbnail of Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

Journal of Endocrinology, 2012

Adiponectin is positively correlated with longevity and negatively correlated with many obesity-r... more Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our res...

Research paper thumbnail of Growth Hormone (GH) Binding and Effects of GH Analogs in Transgenic Mice

Experimental Biology and Medicine, 1994

... o,t RICHARD W. STEGER,” ANDRZEJ BARTKE,”” DANIEL TURYN , ~ CLAUDIO C. AGUILAR,~ ANA I. SOTE D... more ... o,t RICHARD W. STEGER,” ANDRZEJ BARTKE,”” DANIEL TURYN , ~ CLAUDIO C. AGUILAR,~ ANA I. SOTE Department of Physiology, * Southern Illinois University, Carbondale, Illinois 62901; XIAO Z. CHEN,$ AND JOHN J. KOPCHICKS ... 27. Baxter RC, Zaltsman Z, Turtle JR. ...