Modulation of Pituitary Responsiveness to Exogenous LHRH by an Oestrogenic and an Anti-Oestrogenic Compound in the Normal Male (original) (raw)
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European journal of endocrinology, 1979
In normal females, the injection of 25 \g=m\g of LH-RH (acute test) induced a greater LH and FSH release from the pituitary in the mid-luteal than in the mid-follicular phase of the menstrual cycle. In normal males, the responsiveness to 25 \g=m\g LH-RH was greater than that in females at mi d\x=req-\ follicular but not at the luteal stage. The pituitary response to the prolonged LH-RH infusion (0.21 \g=m\g/min/8h) was similar in both phases of the cycle of the females with a decline in serum gonadotrophins after the 4th hour and was paralleled by a significant increase of plasma oestradiol levels. In males the LH, but not the FSH secretion was lower as compared to female subjects, and gonadotrophin levels did not show a fall during the infusion. The acute injection of 25 \g=m\g LH-RH at the end of a prolonged infusion induced the same response in the female subjects in both phases of the cycle. In males, the acute test following prolonged infusion produced a similar LH secretion, but a lower FSH response than in females. The comparison of the acute test alone and that preceded by a prolonged LH-RH infusion, demonstrated that, in females, the only significant differences consisted of a greater LH secretion in the former test in the mid-luteal phase. In males there was greater FSH secretion in the acute isolated test than when this test was given after the prolonged infusion.
BJOG: An International Journal of Obstetrics & Gynaecology, 1975
SummaryThe pituitary responsiveness to synthetic luteinizing hormone releasing hormone (LH‐RH) in female patients with primary and secondary hypogonadism was tested and compared with that in normal women with regular menstrual cycles. A 200 μg dose of synthetic LH‐RH was injected intravenously into 15 normal menstruating women, 8 patients with primary hypogonadism and 5 patients with secondary hypogonadism and the serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) response to LH‐RH was investigated using double‐antibody radioimmunoassay. In normal women, the LH response to LH‐RH in the pre‐ovulatory phase was greater than that seen in the follicular (p<0.05) and luteal phases (p<0.05) of the menstrual cycle. In contrast, no significant difference in the FSH response was demonstrated among the three different phases of the cycle. The serum LH response to LH‐RH in primary hypogonadism was greater than that in the follicular (p<0.01) and luteal phases (p<...
Pituitary response to exogenous LHRH in superovulated women
Reproduction, 1989
The response of the pituitary to exogenous LHRH was investigated in 9 normally ovulating women during the late follicular phase of a spontaneous (control) cycle, a cycle during treatment with clomiphene and a cycle during treatment with 'pure' FSH. During clomiphene treatment, basal FSH concentrations increased significantly up to Day 6 of the cycle and then decreased progressively while basal LH values showed a continuous rise. During treatment with FSH, basal LH concentrations decreased significantly. The response of both FSH and LH to LHRH showed a significant and quantitatively similar decrease during clomiphene or FSH administration as compared to the spontaneous cycles. It is suggested that basal secretion of FSH and LH is regulated by two separate mechanisms, and that an ovarian inhibitory factor(s) attenuates the response of both FSH and LH to exogenous LHRH and possibly the endogenous LH surge in superovulated cycles.
Journal of Endocrinology, 1974
SUMMARY The role of ovarian hormones in the development of increased sensitivity of the anterior pituitary gland to synthetic luteinizing hormone releasing factor (LH-RF) which occurs before and during the preovulatory surge of luteinizing hormone (LH) in the rat has been examined. The response of the pituitary gland was determined, with respect to the secretion of LH and follicle-stimulating hormone (FSH), after the intravenous injection of 50 ng LH-RF/100 g body weight. The LH-RF was injected 30–60 min after the administration of sodium pentobarbitone at either 13.30 h or 18.80 h of pro-oestrus. Blood samples were collected immediately before and at frequent intervals after the injection of LH-RF, and the concentration of LH and FSH in these samples was measured by radioimmunoassay. Ovariectomy at 10.00–11.00 h of dioestrus reduced the LH response to LH-RF injected at 14.00 h of pro-oestrus, while oestradiol benzoate administered immediately after ovariectomy restored and even aug...
Clinical Endocrinology, 1987
LH pulse secretion changes during the menstrual cycle from a rapid regular pattern in the follicular phase to a slower and irregular pattern in the luteal phase. To determine whether the irregular LH pulse pattern in the luteal phase reflects altered GnRH secretion or altered pituitary responsiveness to GnRH, we gave low dose GnRH pulses (25 ng/kg i.v.) every 2 h or every hour for 10 or 12 d to three women with isolated GnRH deficiency. After 4 d of GnRH alone, oestradiol (E2) was given and after 6 d progesterone (P) was added to mimic the hormonal milieu of the luteal phase. LH and FSH were measured every 4 h throughout and also every 20 min for 6 or 12 h, before and after GnRH alone (day 0 and day 4), after E2 (day 6), and after E2+P (day 10 and day 12). Both GnRH pulse frequencies resulted in a rapid increase in plasma FSH to peaks on day 4 (every 2 h) and day 2 and 3 (every hour). FSH concentrations then declined as plasma E2 rose to 50-80 pg/ml reflecting the selective inhibitory effect of E2 on FSH release. Plasma LH was also increased after the hourly GnRH injections and this regimen was associated with a more rapid rise in E2 reflecting follicular maturation. In contrast to the differences in mean hormone concentrations, administration of GnRH at both frequencies resulted in sustained one-on-one responsiveness of LH that was maintained in the presence of both oestrogen and progesterone at mid-luteal phase concentrations. We conclude that the slow frequency of LH pulses observed during the luteal phase reflects decreased GnRH pulse frequency rather than impaired pituitary responsiveness to GnRH.
Endocrinology, 1985
Steroid hormones can differentially modify gonadotropin release stimulated by GnRH. Decreased GnRHmediated gonadotropin release has been observed in vitro after pretreatment with androgens or glucocorticoids. In this study, we tested this phenomenon further with the use of a new cytochemical stain for a potent biotinylated analog of GnRH ([Biotinyl D-Lys 6 ]GnRH) combined with stains for LH and FSH and gonadotropin RIAs. The first phase of the study involved characterization of the GnRH target cells in monolayer cultures from male rats. Dose-response curves (measured as the ability to release both LH and FSH) showed that biotinylated GnRH (Bio-GnRH) was equipotent with or more potent than unlabeled [D-Lys 6 ]GnRH in parallel cultures. The avidin-biotin complex stain demonstrated that 16% of the 2-to 3-day pituitary monolayer cells were labeled for Bio-GnRH within 10 min of exposure. Double stains for gonadotropins showed that 37% of the LH gonadotropes and 42% of the FSH gonadotropes did not stain for Bio-GnRH. During the second phase of these studies, the cultures were pretreated for 48 h with 1-100 nM 5a-dihydrotes-tosterone (DHT), 100 nM corticosterone (CT), or 100 nM epitestosterone (ET) to test the effects of these steroids on the number of cells to which Bio-GnRH bound and the gonadotrope secretory response. Compared with ET-or vehicle-pretreated control cultures, DHT and CT both reduced the amount of LH and FSH release stimulated by GnRH. The magnitude of the reduction in LH release was much greater than that in FSH release, especially after pretreatment with CT. DHT and CT had remarkably different effects on the percentages of cells stained for GnRH. Pretreatment with DHT caused a reduction in the percentages of cells staining for bound Bio-GnRH to 9% compared with 14.3% after CT treatment and 16% after vehicle or ET treatment. The counts of the stained gonadotropes suggested that most of the reduction occurred in the LH gonadotrope population. Because both DHT and CT reduced GnRH-mediated gonadotropin release, but only DHT reduced the percentage of cells that bound Bio-GnRH, it is suggested that the two steroids affect gonadotropin release by separate mechanisms. (Endocrinobgy 117: 396-404,1985) G ONADOTROPES in the anterior pituitary are controlled by GnRH produced in the hypothalamus, whose action is modulated further by gonadal and adrenal steroids. It is generally believed that significant feedback by these steroids occurs directly in the anterior pituitary (1). Negative feedback by testosterone or its active metabolite 5a-dihydrotestosterone (DHT) suppresses GnRH-mediated LH release (2). One mechanism for this suppression is by a reduction in the number of GnRH receptors (3, 4). Recent studies have measured a
Human Reproduction, 2004
BACKGROUND: The purpose of this study was to investigate changes in pituitary response to GnRH in postmenopausal women during substitution treatment with exogenous estrogen and progesterone. METHODS: Seven healthy post-menopausal women (group 1) were treated with various doses of E 2 valerate for 43 days, so as the serum concentrations of E 2 mimicked those of a follicular (FP-1), a luteal (LP) and a second follicular (FP-2) phase. During the LP, progesterone was also administered. The 30 min response of LH (DLH) and FSH (DFSH) to GnRH (10 mg i.v.) (pituitary sensitivity) was investigated every 24 h in group 1 and also in seven normally cycling women (group 2) during a spontaneous (control) follicular phase (FP). Based on the hormone profiles, day 32 in group 1 (FP-2) corresponded to day 2 in the spontaneous FP of group 2. RESULTS: Basal FSH concentrations were significantly higher in FP-2 than in the control FP (P < 0.05), while basal LH concentrations were similar in the two phases with higher values in FP-2 towards the end of the experiment (corresponding to days 10 and 11, P < 0.05). However, an LH surge was seen only in the control FP. DFSH values remained stable in both phases and increased only in the control FP on days 12 and 13. DLH values remained stable in the control FP and only increased on days 12 (P < 0.05) and 13 (P < 0.05), but in FP-2, DLH values increased earlier (corresponding to day 7, P < 0.05). CONCLUSIONS: The present study demonstrates for the first time that in the absence of ovarian function, follicular phase E 2 concentrations sensitize the pituitary to GnRH at an earlier stage (corresponding to the midfollicular phase) than in the normal menstrual cycle (late follicular phase). It is suggested that during the early to midfollicular phase the ovaries produce a gonadotrophin surge attenuating factor (GnSAF) that antagonizes the pituitary-sensitizing effect of E 2 to GnRH.
Journal of Clinical Investigation, 1988
The effects of decreasing the frequency of pulsatile gonadotropin-releasing hormone (GnRH) stimulation on pituitary responsiveness were studied in (a) men with isolated GnRH deficiency who had achieved normal sex steroid levels during prior long-term pulsatile GnRH replacement and (b) perifused dispersed pituitary cells from male rats in the absence of sex steroids. In three groups of four GnRH-deficient men, the frequency of GnRH stimulation was decreased at weekly intervals from (a) every 2-34 h (group I), (b) every 2-8 h without testosterone replacement (group II), or (c) every 2-8 h with testosterone replacement (group III). In three groups of three columns of perifused dispersed pituitary cells, pulses of GnRH were administered every 2, 4, or 8 h.
Endocrinology, 1963
oratory have demonstrated a luteinizing hormone (LH)-releasing action of crude hypothalamic extracts. This conclusion was based on the ability of these extracts to deplete ovarian ascorbic acid in immature rats pretreated with gonadotrophins (1). Since this test animal is highly sensitive to LH, the extract either released LH from the hypophysis of the test animals or contained LH itself as a contaminant. The activity in the extract was heat stable, whereas LH is quite heat labile, which supports the conclusion that LH release had occurred from the pituitaries of the test animals (2). Tests with other substances known to be present in the extract indicated that the activity could not be accounted for by these compounds and suggested that a specific LH-releasing factor (LH-RF) might be present in hypothalamic tissue (1).