N. MacLusky - Academia.edu (original) (raw)

Papers by N. MacLusky

Research paper thumbnail of Metabolism and binding of androgens in the spinal cord of the rat

Brain Research, 1987

The binding of [3H]androgens and estrogens, and the metabolism of [3H]androgens, were studied in ... more The binding of [3H]androgens and estrogens, and the metabolism of [3H]androgens, were studied in the spinal cord of the adult rat. High-affinity, specific binding sites for [3H]testosterone and [3H]estradiol were detected in cytosol fractions from the spinal cords of castrate animals. Equilibrium dissociation constants for reaction of these sites with their respective ligands were similar to those of androgen and estrogen receptors from other regions of the central nervous system. Nuclear binding of [3H]estradiol was observed in the spinal cord 1 h after intravenous administration of the isotope. Likewise, exchange assay demonstrated the presence of high-affinity androgen binding sites in spinal cord nuclei from orchidectomized, testosterone propionate treated animals. 5a-Reductase activity in homogenates of the spinal cord was relatively high, approximately 3 times that in the pooled hypothalamus, preoptic area, septum and amygdala. However, in contrast to the latter brain regions, estrogen formation was not detectable in spinal cord tissue. No sex differences were observed in the metabolism of [3H]testosterone by spinal cord homogenates. These results confirm the presence of androgen and estrogen receptors in the rat spinal cord. The lack of detectable aromatase activity in the spinal cord is consistent with the hypothesis that the effects of circulating testosterone on spinal reflex function are mediated primarily through the androgen receptor system.

Research paper thumbnail of Intrinsic tyrosine hydroxylase (TH) immunoreactive axons synapse with TH immunopositive neurons in the rat arcuate nucleus

Brain Research, 1985

Synaptic connections were demonstrated between tyrosine hydroxylase (TH) immunoreactive axons and... more Synaptic connections were demonstrated between tyrosine hydroxylase (TH) immunoreactive axons and dendrites in the arcuate nucleus of the rat, by electron microscopic immunocytochemistry. These connections were primarily found in the lateral part of the nucleus. The results of two types of medial-dorsal-lateral surgical de-afferentation suggest that the TH-TH contacts represent intrinsic connections.

Research paper thumbnail of The periovulatory and luteal phase of conception cycles following in vitro fertilization and embryo transfer

Fertility and Sterility, 1984

The pattern of periovulatory and luteal phase levels of serum estradiol (E,J and progesterone (P)... more The pattern of periovulatory and luteal phase levels of serum estradiol (E,J and progesterone (P) were compared between 8 conception and 28 nonconception cycles of patients undergoing in vitro fertilization (lVF). Ten additional women served as control subjects and did not undergo follicular aspiration. Follicle growth was induced with an individualized Pergonal (human menopausal gonadotropin) regimen, and laparoscopy was performed 36 hours after human chorionic gonadotropin administration. The length of the luteal phase did not differ significantly among the three groups and was between 14 and 15 days in duration. When IVF conception cycles were compared with nonconception cycles, although no difference in the number of large follicles was observed (4.25 ± 0.45 versus 3.6 ± 0.25), the patterns of E2 and P differed significantly. Daily serum E2 levels tended to be higher in the periovulatory phase in conception cycles when compared with nonconception cycles, and were significantly (P < 0.05) higher in the early, mid, and late luteal phases. Serum P levels were significantly higher (P < 0.05) in conception cycles from the midluteal phase onward. A decline in both serum E2 and P in the midluteal phase in conception cycles suggested some degree of corpus luteum deficiency. It is suggested that high E2 levels in the periovulatory phase may be an indicator of better follicular development under human menopausal gonadotropin stimulation and that the deficiency observed in the late luteal phase is overcome with the establishment of pregnancy.

Research paper thumbnail of Idle thoughts of idle pharmacologists

Advances in the biosciences, 1973

Research paper thumbnail of Histopathologic correlations of estrogen and progestin receptor protein in epithelial ovarian carcinomas

Obstetrics and gynecology, 1985

One hundred thirteen primary epithelial ovarian cancers were analyzed for estrogen and progestin ... more One hundred thirteen primary epithelial ovarian cancers were analyzed for estrogen and progestin receptor content and the results compared with multiple histologic parameters (grade, necrosis, fibrosis, lymphocyte infiltration, mitoses, tumor giant cells, psammoma bodies, stroma). Grade 4 cancers had a statistically greater likelihood of containing estrogen receptors (P = .03) than did lower grade cancers. However, grade 3 tumor samples containing abundant (3+ and 4+) mitoses had a significantly greater number of estrogen receptor negative cancers (P = .01) than did cancers containing none to moderate (0-2+) mitoses. The only histologic parameter that demonstrated any statistically significant association with progestin receptor content was the presence of lymphocyte infiltration. Samples demonstrating moderate (2+ and 3+) lymphocyte infiltration had a significantly (P = .005) greater chance of being progestin receptor negative than cancers containing none to minimal (0 to 1+) lymph...

Research paper thumbnail of Circannual rhythms in steroid receptor concentration in gynecologic and breast cancers

American Journal of Obstetrics and Gynecology, 1987

Both estrogen and progestin receptor concentrations vary in a predictive temporal pattern for bre... more Both estrogen and progestin receptor concentrations vary in a predictive temporal pattern for breast cancer; in epithelial ovarian cancer a temporal rhythmic pattern is suggested for estrogen receptor concentration only. No pattern for either receptor is seen for endometrial cancer.

Research paper thumbnail of Rapid Microcomputer-Based Analysis of Semen Characteristics from Photographs Taken by the MEP Method

Systems Biology in Reproductive Medicine, 1984

Use of a microcomputer with the multiple exposure photography (MEP) method for rapid analysis of ... more Use of a microcomputer with the multiple exposure photography (MEP) method for rapid analysis of semen characteristics is described. The computer is programmed to calculate information fed from a digitizing tablet while scanning projected images of photographed sperm. In this way sperm concentration, percentage of motility, average velocity and frequency distribution of sperm velocity, as well as percentage of abnormal forms are immediately obtained. The method was found to be as accurate, less prone to error, and significantly less time consuming than the previous manual measuring method. It can greatly facilitate routine semen analysis in laboratories using the MEP method.

Research paper thumbnail of Solitary pelvic neural tumors with high steroid receptor content

Gynecologic Oncology, 1985

Two pelvic benign neural tumors, a neurofibroma and a neurilemmoma, were found to have high level... more Two pelvic benign neural tumors, a neurofibroma and a neurilemmoma, were found to have high levels of cell nuclear estrogen receptors and both cytoplasmic and nuclear progestin receptors. A review of the literature reveals that neurogenic tumors occur predominantly in young women. This observation together with the recent findings of elevated sex steroid receptor proteins in meningiomas supports a hypothesis for the common hormonal dependence of neoplasms arising from the neural supporting tissues.

Research paper thumbnail of Limbic Seizures Alter Reproductive Function in the Female Rat

Epilepsia, 1999

Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilep... more Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilepsy. This study used the kindled rat model to test the hypothesis that limbic seizures directly contribute to reproductive dysfunction. Kindling electrodes were implanted in the basolateral amygdala in adult female rats. Females were kindled by either brief, daily, suprathreshold stimulations with a bipolar electrode or sham-kindled (controls). Electrographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears. Seizures arrested ovarian cyclicity in all (n = 42) kindled animals, the rats exhibiting persistent vaginal cornification (PVC). In these animals PVC was associated with high serum estradiol, increased pituitary weight, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, this effect occurred after the development of stage 5 motor seizures, when focal seizures had secondarily generalized. In contrast, only five (21%) of 24 sham-kindled controls exhibited PVC. A single injection of progesterone (P4) temporarily restored cyclicity in five (18%) of 28 kindled females exhibiting PVC. In contrast, P4 administration restored cyclicity in all five sham-kindled controls that had spontaneously stopped cycling. P4 treatment to kindled females in PVC resulted in a different endocrine profile than that in non-P4-treated, kindled rats in PVC. P4-treated rats had high serum estradiol, testosterone, and prolactin levels; they showed an increase in pituitary weight; and their ovaries contained numerous corpora lutea and cystic follicles surrounded by markedly overdeveloped thecal cell layers. Seizures initiated in the amygdala result in impairment of the hypothalamic-pituitary axis, resulting in loss of ovarian cyclicity.

Research paper thumbnail of Estrogen formation in the mammalian brain: Possible role of aromatase in sexual differentiation of the hippocampus and neocortex

Steroids, 1987

Recent studies su effects of circulating an gest that sex differences in cognitive function may i... more Recent studies su effects of circulating an gest that sex differences in cognitive function may involve jf ro ens on the developing cerebral cortex and hippocampus. The mechanism of these e fects is not understood. In rhesus monkeys, aromatase activity is present in the hip late fetal and early postnata P. ocampus and several areas of the cerebral cortex during hfe. Similarly, work in rats and mice indicates that the hippocampus and cerebral cortex may be capable of estrogen biosynthesis during early development. These results are consistent with the hypothesis that the actions of androgens on the developin f cerebral cortex and hippocam estrogen-mediated effects simi ar to those resnonsible for $ us may involve local tfferentiation of the hypo;halamic mechanisms controlling reproductiie function.

Research paper thumbnail of Sexual differentiation of the central nervous system

Science, 1981

Sexual differentiation of reproductive and behavior patterns is largely effected by hormones prod... more Sexual differentiation of reproductive and behavior patterns is largely effected by hormones produced by the gonads. In many higher vertebrates, an integral part of this process is the induction of permanent and essentially irreversible sex differences in central nervous function, in response to gonadal hormones secreted early in development.

Research paper thumbnail of 221. Metabolic clearance rates of 4-hydroxyestrogens in man

Journal of Steroid Biochemistry, 1982

Research paper thumbnail of The naturally occurring C-17 fatty acid esters of estradiol are long-acting estrogens

Journal of steroid biochemistry, 1985

C-17 fatty acid esters of estradiol are naturally occurring biosynthetic metabolites of estradiol... more C-17 fatty acid esters of estradiol are naturally occurring biosynthetic metabolites of estradiol. A representative component of this family of esters, estradiol-17-stearate, was studied in order to determine the estrogenic properties of these unusual hydrophobic steroids. Following the classical estrogen bioassay, a solution of this ester in oil was injected subcutaneously into immature rats once a day for 3 days. There was little effect on the uterus on the first day after the third injection. However, on subsequent days a large stimulation of uterine growth occurred. The course of this estrogenic effect was exactly opposite to that obtained with estradiol. In order to eliminate the possibility that this effect on the time course of estrogenic stimulation was caused by increased solubility of the hydrophobic esters in the carrier oil, the steroids were administered to adult ovariectomized animals in aqueous medium via a single intravenous injection. The uterotrophic response to es...

Research paper thumbnail of A study of cytoplasmic and nuclear estrogen and progestin receptors in gynecologic neoplasms

Endocrinologia japonica, 1987

A rapid method for simultaneous preparation of cytosol and nuclear estrogen (E) and progestin (P)... more A rapid method for simultaneous preparation of cytosol and nuclear estrogen (E) and progestin (P) receptors and their in vitro determination is described. The method was applied to several uterine or ovarian surgical specimens to evaluate their steroid hormone "dependence". The results suggest that low cytoplasmic E receptor levels (ERc) are associated with higher nuclear E receptor (ERn) levels but no apparent correlation was observed between PRc and ERn levels. The method appeared to be suitable for screening steroid hormone receptor content in tumor tissues and may provide better estimation of steroid dependence since both cytoplasmic and nuclear compartments can be studied simultaneously.

Research paper thumbnail of Cytoplasmic and nuclear estradiol-17 beta binding in male and female rat brain: regional distribution, temporal aspects and metabolism

Brain research, Jan 14, 1980

A study was conducted in which we simultaneously measured absolute levels of cell nuclear estradi... more A study was conducted in which we simultaneously measured absolute levels of cell nuclear estradiol-17 beta (E2) retention and cytosol E2 saturation binding capacities in various neural tissues from adult gonadectomized-adrenalectomized (GX-ADX) male and female rats, at various times after a saturating dose of [3H]E2. The results indicate that, with minor exceptions, the basic properties of E2 metabolism and E2 retention kinetics in target brain tissues and corresponding cell nuclear and cytosol fractions are quite similar in GX-ADX male and female rats. The results do not, however, rule out the possibility of subtle sex differences in estrogen binding in at least some brain regions which were studied. The present demonstration of E2 binding in various regions of the male brain is consistent with a physiological role of estrogen in the male; however, the similarities in these E2 binding parameters between the sexes unfortunately shed little light on the marked neuroendocrine sex dif...

Research paper thumbnail of Tamoxifen therapy for advanced ovarian cancer

Obstetrics and gynecology, 1982

Thirteen patients with rapidly advancing recurrent epithelial ovarian cancers, in whom chemothera... more Thirteen patients with rapidly advancing recurrent epithelial ovarian cancers, in whom chemotherapy and, in some cases, radiation therapy failed, were treated with the estrogen antagonist tamoxifen. The presence of cytosol estrogen receptors, which have recently been identified in ovarian cancer specimens, was determined in the tumor from each patient prior to tamoxifen treatment. No complete responses were observed. One patient had a partial response and 4 patients had prolonged stabilization of disease. All patients with stabilized disease had estrogen receptor levels that were borderline or high. Eight patients demonstrated no response to oral tamoxifen therapy, but 5 of these had partial small bowel obstruction secondary to advanced recurrent cancer. As tamoxifen in this preliminary study may have stabilized rapidly advancing recurrent ovarian cancer in combination with cytotoxic chemotherapy should be considered.

Research paper thumbnail of Asynchrony between human cumulus-corona cell complex and oocyte maturation after human menopausal gonadotropin treatment for in vitro fertilization

Fertility and sterility, 1984

One hundred seventeen oocyte-cumulus-corona cell complexes (CCCs) were obtained from 15 women und... more One hundred seventeen oocyte-cumulus-corona cell complexes (CCCs) were obtained from 15 women undergoing in vitro fertilization after human menopausal gonadotropin/human chorionic gonadotropin follicular stimulation. In each woman, five oocyte-CCCs were left intact, and the remaining one to five oocytes were freed of their CCCs by hyaluronidase (300 IU/ml) dispersal treatment. Dispersal time for individual CCCs correlated well with their degree of mucification and was significantly shorter in 20 mature CCCs as compared with 24 intermediate CCCs (1.20 +/- 0.05 versus 2.35 +/- 0.13 minutes, respectively; P less than 0.001). Oocyte maturation at collection and after 8 hours of in vitro incubation was not related to the CCC type present at harvest. Maturation of oocytes progressed regardless of CCC type; so that after 8 hours of preincubation, 73% of the oocytes attained a polar body while 20% were still at the germinal vesicle breakdown stage and 7% at the germinal vesicle stage. Overa...

Research paper thumbnail of The cellular effects of estrogens on neuroendocrine tissues

Journal of steroid biochemistry, 1988

Estrogen action on sensitive neurons in the rat diencephalon has been studied by morphologic tech... more Estrogen action on sensitive neurons in the rat diencephalon has been studied by morphologic techniques; evidence of estrogen action at every level is presented, including tracts, cells, circuitry and subcellular organelles. The demonstration in the arcuate nucleus of estrogen-induced synaptic remodelling, estrogen-induced postsynaptic membrane phenotypes, changes in intracellular membranes and rapid estrogen actions on neuronal endo-exocytosis indicates that cellular estrogen actions may underlie the neuronal control of reproduction.

Research paper thumbnail of Aromatization and Development of Responsiveness of the Brain to Gonadal Steroids

Development of Responsiveness to Steroid Hormones, 1980

Research paper thumbnail of 291. Aromatase activity in ovarian cancer

Journal of Steroid Biochemistry, 1982

Recently we presented evidence based on tissue culture studies which suggested that at least in f... more Recently we presented evidence based on tissue culture studies which suggested that at least in fetal life, ll-hydroxysteroid dehydrogenase (1lHSD) comprises two (or more) enzymes-one which is exclusively oxidative, residing in epithelial-like fetal lung cells, and one which is mainly reductive, present in fibrobast-like cells (J. Clin. Endocrinol. Metab. 54:563, 1982). Factors controlling the enzyme activity in $k ese cel.Ls are unknown. Studies were carried out using equimolar 3H-cortisol and C-cortisone added daily to explant and monolayer cultures of human fetal lung cells at lo-20 weeks gestation. The medium was extracted, chromatographed on Sephadex LH-20 to separate cortisol and cortisone, and the substrate conversion calculated as cpm(product) x lOO/cpm(product + substrate). The following were added in physiological amounts for 3 days: hCG, ACTH, prolactin, placental lactogen, triiodothyronine, progesterone, estrone, estradiol, estriol, placental medium, oxytocin, and adrenal extracts; and the cultures were also grown under low oxygen tension. The oxidative enzyme in explant culture was affected very little by any of ehese while the reductive enzyme was stimulated by hCG, adrenal extracts and placental medium. Fibroblast growth was increased by low oxygen. The results show that the enzyme activity of the fibroblast-like cells responds differently to that of the epithelial-like cells.

Research paper thumbnail of Metabolism and binding of androgens in the spinal cord of the rat

Brain Research, 1987

The binding of [3H]androgens and estrogens, and the metabolism of [3H]androgens, were studied in ... more The binding of [3H]androgens and estrogens, and the metabolism of [3H]androgens, were studied in the spinal cord of the adult rat. High-affinity, specific binding sites for [3H]testosterone and [3H]estradiol were detected in cytosol fractions from the spinal cords of castrate animals. Equilibrium dissociation constants for reaction of these sites with their respective ligands were similar to those of androgen and estrogen receptors from other regions of the central nervous system. Nuclear binding of [3H]estradiol was observed in the spinal cord 1 h after intravenous administration of the isotope. Likewise, exchange assay demonstrated the presence of high-affinity androgen binding sites in spinal cord nuclei from orchidectomized, testosterone propionate treated animals. 5a-Reductase activity in homogenates of the spinal cord was relatively high, approximately 3 times that in the pooled hypothalamus, preoptic area, septum and amygdala. However, in contrast to the latter brain regions, estrogen formation was not detectable in spinal cord tissue. No sex differences were observed in the metabolism of [3H]testosterone by spinal cord homogenates. These results confirm the presence of androgen and estrogen receptors in the rat spinal cord. The lack of detectable aromatase activity in the spinal cord is consistent with the hypothesis that the effects of circulating testosterone on spinal reflex function are mediated primarily through the androgen receptor system.

Research paper thumbnail of Intrinsic tyrosine hydroxylase (TH) immunoreactive axons synapse with TH immunopositive neurons in the rat arcuate nucleus

Brain Research, 1985

Synaptic connections were demonstrated between tyrosine hydroxylase (TH) immunoreactive axons and... more Synaptic connections were demonstrated between tyrosine hydroxylase (TH) immunoreactive axons and dendrites in the arcuate nucleus of the rat, by electron microscopic immunocytochemistry. These connections were primarily found in the lateral part of the nucleus. The results of two types of medial-dorsal-lateral surgical de-afferentation suggest that the TH-TH contacts represent intrinsic connections.

Research paper thumbnail of The periovulatory and luteal phase of conception cycles following in vitro fertilization and embryo transfer

Fertility and Sterility, 1984

The pattern of periovulatory and luteal phase levels of serum estradiol (E,J and progesterone (P)... more The pattern of periovulatory and luteal phase levels of serum estradiol (E,J and progesterone (P) were compared between 8 conception and 28 nonconception cycles of patients undergoing in vitro fertilization (lVF). Ten additional women served as control subjects and did not undergo follicular aspiration. Follicle growth was induced with an individualized Pergonal (human menopausal gonadotropin) regimen, and laparoscopy was performed 36 hours after human chorionic gonadotropin administration. The length of the luteal phase did not differ significantly among the three groups and was between 14 and 15 days in duration. When IVF conception cycles were compared with nonconception cycles, although no difference in the number of large follicles was observed (4.25 ± 0.45 versus 3.6 ± 0.25), the patterns of E2 and P differed significantly. Daily serum E2 levels tended to be higher in the periovulatory phase in conception cycles when compared with nonconception cycles, and were significantly (P < 0.05) higher in the early, mid, and late luteal phases. Serum P levels were significantly higher (P < 0.05) in conception cycles from the midluteal phase onward. A decline in both serum E2 and P in the midluteal phase in conception cycles suggested some degree of corpus luteum deficiency. It is suggested that high E2 levels in the periovulatory phase may be an indicator of better follicular development under human menopausal gonadotropin stimulation and that the deficiency observed in the late luteal phase is overcome with the establishment of pregnancy.

Research paper thumbnail of Idle thoughts of idle pharmacologists

Advances in the biosciences, 1973

Research paper thumbnail of Histopathologic correlations of estrogen and progestin receptor protein in epithelial ovarian carcinomas

Obstetrics and gynecology, 1985

One hundred thirteen primary epithelial ovarian cancers were analyzed for estrogen and progestin ... more One hundred thirteen primary epithelial ovarian cancers were analyzed for estrogen and progestin receptor content and the results compared with multiple histologic parameters (grade, necrosis, fibrosis, lymphocyte infiltration, mitoses, tumor giant cells, psammoma bodies, stroma). Grade 4 cancers had a statistically greater likelihood of containing estrogen receptors (P = .03) than did lower grade cancers. However, grade 3 tumor samples containing abundant (3+ and 4+) mitoses had a significantly greater number of estrogen receptor negative cancers (P = .01) than did cancers containing none to moderate (0-2+) mitoses. The only histologic parameter that demonstrated any statistically significant association with progestin receptor content was the presence of lymphocyte infiltration. Samples demonstrating moderate (2+ and 3+) lymphocyte infiltration had a significantly (P = .005) greater chance of being progestin receptor negative than cancers containing none to minimal (0 to 1+) lymph...

Research paper thumbnail of Circannual rhythms in steroid receptor concentration in gynecologic and breast cancers

American Journal of Obstetrics and Gynecology, 1987

Both estrogen and progestin receptor concentrations vary in a predictive temporal pattern for bre... more Both estrogen and progestin receptor concentrations vary in a predictive temporal pattern for breast cancer; in epithelial ovarian cancer a temporal rhythmic pattern is suggested for estrogen receptor concentration only. No pattern for either receptor is seen for endometrial cancer.

Research paper thumbnail of Rapid Microcomputer-Based Analysis of Semen Characteristics from Photographs Taken by the MEP Method

Systems Biology in Reproductive Medicine, 1984

Use of a microcomputer with the multiple exposure photography (MEP) method for rapid analysis of ... more Use of a microcomputer with the multiple exposure photography (MEP) method for rapid analysis of semen characteristics is described. The computer is programmed to calculate information fed from a digitizing tablet while scanning projected images of photographed sperm. In this way sperm concentration, percentage of motility, average velocity and frequency distribution of sperm velocity, as well as percentage of abnormal forms are immediately obtained. The method was found to be as accurate, less prone to error, and significantly less time consuming than the previous manual measuring method. It can greatly facilitate routine semen analysis in laboratories using the MEP method.

Research paper thumbnail of Solitary pelvic neural tumors with high steroid receptor content

Gynecologic Oncology, 1985

Two pelvic benign neural tumors, a neurofibroma and a neurilemmoma, were found to have high level... more Two pelvic benign neural tumors, a neurofibroma and a neurilemmoma, were found to have high levels of cell nuclear estrogen receptors and both cytoplasmic and nuclear progestin receptors. A review of the literature reveals that neurogenic tumors occur predominantly in young women. This observation together with the recent findings of elevated sex steroid receptor proteins in meningiomas supports a hypothesis for the common hormonal dependence of neoplasms arising from the neural supporting tissues.

Research paper thumbnail of Limbic Seizures Alter Reproductive Function in the Female Rat

Epilepsia, 1999

Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilep... more Reproductive dysfunction and endocrine disorders are common among women with temporal lobe epilepsy. This study used the kindled rat model to test the hypothesis that limbic seizures directly contribute to reproductive dysfunction. Kindling electrodes were implanted in the basolateral amygdala in adult female rats. Females were kindled by either brief, daily, suprathreshold stimulations with a bipolar electrode or sham-kindled (controls). Electrographic and behavioral seizures were monitored. Estrous cycles also were monitored with daily vaginal smears. Seizures arrested ovarian cyclicity in all (n = 42) kindled animals, the rats exhibiting persistent vaginal cornification (PVC). In these animals PVC was associated with high serum estradiol, increased pituitary weight, and polyfollicular ovaries consisting of many cystic follicles, as well as follicles in various stages of growth and atresia. In 93% of females, this effect occurred after the development of stage 5 motor seizures, when focal seizures had secondarily generalized. In contrast, only five (21%) of 24 sham-kindled controls exhibited PVC. A single injection of progesterone (P4) temporarily restored cyclicity in five (18%) of 28 kindled females exhibiting PVC. In contrast, P4 administration restored cyclicity in all five sham-kindled controls that had spontaneously stopped cycling. P4 treatment to kindled females in PVC resulted in a different endocrine profile than that in non-P4-treated, kindled rats in PVC. P4-treated rats had high serum estradiol, testosterone, and prolactin levels; they showed an increase in pituitary weight; and their ovaries contained numerous corpora lutea and cystic follicles surrounded by markedly overdeveloped thecal cell layers. Seizures initiated in the amygdala result in impairment of the hypothalamic-pituitary axis, resulting in loss of ovarian cyclicity.

Research paper thumbnail of Estrogen formation in the mammalian brain: Possible role of aromatase in sexual differentiation of the hippocampus and neocortex

Steroids, 1987

Recent studies su effects of circulating an gest that sex differences in cognitive function may i... more Recent studies su effects of circulating an gest that sex differences in cognitive function may involve jf ro ens on the developing cerebral cortex and hippocampus. The mechanism of these e fects is not understood. In rhesus monkeys, aromatase activity is present in the hip late fetal and early postnata P. ocampus and several areas of the cerebral cortex during hfe. Similarly, work in rats and mice indicates that the hippocampus and cerebral cortex may be capable of estrogen biosynthesis during early development. These results are consistent with the hypothesis that the actions of androgens on the developin f cerebral cortex and hippocam estrogen-mediated effects simi ar to those resnonsible for $ us may involve local tfferentiation of the hypo;halamic mechanisms controlling reproductiie function.

Research paper thumbnail of Sexual differentiation of the central nervous system

Science, 1981

Sexual differentiation of reproductive and behavior patterns is largely effected by hormones prod... more Sexual differentiation of reproductive and behavior patterns is largely effected by hormones produced by the gonads. In many higher vertebrates, an integral part of this process is the induction of permanent and essentially irreversible sex differences in central nervous function, in response to gonadal hormones secreted early in development.

Research paper thumbnail of 221. Metabolic clearance rates of 4-hydroxyestrogens in man

Journal of Steroid Biochemistry, 1982

Research paper thumbnail of The naturally occurring C-17 fatty acid esters of estradiol are long-acting estrogens

Journal of steroid biochemistry, 1985

C-17 fatty acid esters of estradiol are naturally occurring biosynthetic metabolites of estradiol... more C-17 fatty acid esters of estradiol are naturally occurring biosynthetic metabolites of estradiol. A representative component of this family of esters, estradiol-17-stearate, was studied in order to determine the estrogenic properties of these unusual hydrophobic steroids. Following the classical estrogen bioassay, a solution of this ester in oil was injected subcutaneously into immature rats once a day for 3 days. There was little effect on the uterus on the first day after the third injection. However, on subsequent days a large stimulation of uterine growth occurred. The course of this estrogenic effect was exactly opposite to that obtained with estradiol. In order to eliminate the possibility that this effect on the time course of estrogenic stimulation was caused by increased solubility of the hydrophobic esters in the carrier oil, the steroids were administered to adult ovariectomized animals in aqueous medium via a single intravenous injection. The uterotrophic response to es...

Research paper thumbnail of A study of cytoplasmic and nuclear estrogen and progestin receptors in gynecologic neoplasms

Endocrinologia japonica, 1987

A rapid method for simultaneous preparation of cytosol and nuclear estrogen (E) and progestin (P)... more A rapid method for simultaneous preparation of cytosol and nuclear estrogen (E) and progestin (P) receptors and their in vitro determination is described. The method was applied to several uterine or ovarian surgical specimens to evaluate their steroid hormone "dependence". The results suggest that low cytoplasmic E receptor levels (ERc) are associated with higher nuclear E receptor (ERn) levels but no apparent correlation was observed between PRc and ERn levels. The method appeared to be suitable for screening steroid hormone receptor content in tumor tissues and may provide better estimation of steroid dependence since both cytoplasmic and nuclear compartments can be studied simultaneously.

Research paper thumbnail of Cytoplasmic and nuclear estradiol-17 beta binding in male and female rat brain: regional distribution, temporal aspects and metabolism

Brain research, Jan 14, 1980

A study was conducted in which we simultaneously measured absolute levels of cell nuclear estradi... more A study was conducted in which we simultaneously measured absolute levels of cell nuclear estradiol-17 beta (E2) retention and cytosol E2 saturation binding capacities in various neural tissues from adult gonadectomized-adrenalectomized (GX-ADX) male and female rats, at various times after a saturating dose of [3H]E2. The results indicate that, with minor exceptions, the basic properties of E2 metabolism and E2 retention kinetics in target brain tissues and corresponding cell nuclear and cytosol fractions are quite similar in GX-ADX male and female rats. The results do not, however, rule out the possibility of subtle sex differences in estrogen binding in at least some brain regions which were studied. The present demonstration of E2 binding in various regions of the male brain is consistent with a physiological role of estrogen in the male; however, the similarities in these E2 binding parameters between the sexes unfortunately shed little light on the marked neuroendocrine sex dif...

Research paper thumbnail of Tamoxifen therapy for advanced ovarian cancer

Obstetrics and gynecology, 1982

Thirteen patients with rapidly advancing recurrent epithelial ovarian cancers, in whom chemothera... more Thirteen patients with rapidly advancing recurrent epithelial ovarian cancers, in whom chemotherapy and, in some cases, radiation therapy failed, were treated with the estrogen antagonist tamoxifen. The presence of cytosol estrogen receptors, which have recently been identified in ovarian cancer specimens, was determined in the tumor from each patient prior to tamoxifen treatment. No complete responses were observed. One patient had a partial response and 4 patients had prolonged stabilization of disease. All patients with stabilized disease had estrogen receptor levels that were borderline or high. Eight patients demonstrated no response to oral tamoxifen therapy, but 5 of these had partial small bowel obstruction secondary to advanced recurrent cancer. As tamoxifen in this preliminary study may have stabilized rapidly advancing recurrent ovarian cancer in combination with cytotoxic chemotherapy should be considered.

Research paper thumbnail of Asynchrony between human cumulus-corona cell complex and oocyte maturation after human menopausal gonadotropin treatment for in vitro fertilization

Fertility and sterility, 1984

One hundred seventeen oocyte-cumulus-corona cell complexes (CCCs) were obtained from 15 women und... more One hundred seventeen oocyte-cumulus-corona cell complexes (CCCs) were obtained from 15 women undergoing in vitro fertilization after human menopausal gonadotropin/human chorionic gonadotropin follicular stimulation. In each woman, five oocyte-CCCs were left intact, and the remaining one to five oocytes were freed of their CCCs by hyaluronidase (300 IU/ml) dispersal treatment. Dispersal time for individual CCCs correlated well with their degree of mucification and was significantly shorter in 20 mature CCCs as compared with 24 intermediate CCCs (1.20 +/- 0.05 versus 2.35 +/- 0.13 minutes, respectively; P less than 0.001). Oocyte maturation at collection and after 8 hours of in vitro incubation was not related to the CCC type present at harvest. Maturation of oocytes progressed regardless of CCC type; so that after 8 hours of preincubation, 73% of the oocytes attained a polar body while 20% were still at the germinal vesicle breakdown stage and 7% at the germinal vesicle stage. Overa...

Research paper thumbnail of The cellular effects of estrogens on neuroendocrine tissues

Journal of steroid biochemistry, 1988

Estrogen action on sensitive neurons in the rat diencephalon has been studied by morphologic tech... more Estrogen action on sensitive neurons in the rat diencephalon has been studied by morphologic techniques; evidence of estrogen action at every level is presented, including tracts, cells, circuitry and subcellular organelles. The demonstration in the arcuate nucleus of estrogen-induced synaptic remodelling, estrogen-induced postsynaptic membrane phenotypes, changes in intracellular membranes and rapid estrogen actions on neuronal endo-exocytosis indicates that cellular estrogen actions may underlie the neuronal control of reproduction.

Research paper thumbnail of Aromatization and Development of Responsiveness of the Brain to Gonadal Steroids

Development of Responsiveness to Steroid Hormones, 1980

Research paper thumbnail of 291. Aromatase activity in ovarian cancer

Journal of Steroid Biochemistry, 1982

Recently we presented evidence based on tissue culture studies which suggested that at least in f... more Recently we presented evidence based on tissue culture studies which suggested that at least in fetal life, ll-hydroxysteroid dehydrogenase (1lHSD) comprises two (or more) enzymes-one which is exclusively oxidative, residing in epithelial-like fetal lung cells, and one which is mainly reductive, present in fibrobast-like cells (J. Clin. Endocrinol. Metab. 54:563, 1982). Factors controlling the enzyme activity in $k ese cel.Ls are unknown. Studies were carried out using equimolar 3H-cortisol and C-cortisone added daily to explant and monolayer cultures of human fetal lung cells at lo-20 weeks gestation. The medium was extracted, chromatographed on Sephadex LH-20 to separate cortisol and cortisone, and the substrate conversion calculated as cpm(product) x lOO/cpm(product + substrate). The following were added in physiological amounts for 3 days: hCG, ACTH, prolactin, placental lactogen, triiodothyronine, progesterone, estrone, estradiol, estriol, placental medium, oxytocin, and adrenal extracts; and the cultures were also grown under low oxygen tension. The oxidative enzyme in explant culture was affected very little by any of ehese while the reductive enzyme was stimulated by hCG, adrenal extracts and placental medium. Fibroblast growth was increased by low oxygen. The results show that the enzyme activity of the fibroblast-like cells responds differently to that of the epithelial-like cells.