Pituitary LH Secretion Research Articles

Dose Response Effects of Pulsatile GnRH Administration on Restoration of Pituitary GnRH Receptors and Pulsatile LH Secretion during Lactation

Ovariectomized (OVX) rats suckling 8 pups have a complete suppression of pulsatile LH secretion and a decrease in pituitary GnRH receptor (GnRH-R) content. Removing the suckling stimulus for 24 h results in a sharp increase in GnRH-R and a restoration of pulsatile LH secretion. These findings suggest that the suckling stimulus induces a suppression of GnRH secretion, and removal of the suckling stimulus permits the restoration of GnRH secretion. Indeed, if GnRH antiserum is injected at the time of pup removal, the restoration of pituitary GnRH-R and LH secretion is prevented. The present studies were designed to test our hypothesis that the deficits in pituitary gonadotroph function observed during lactation are due to suckling-induced suppression of GnRH. Exogenous GnRH was administered in a pulsatile regimen to OVX lactating rats on days 10 and 11 postpartum, and the effects on pituitary GnRH-R levels, pituitary sensitivity to GnRH, and pulsatile LH secretion were assessed. GnRH doses of 0, 0.5, 2.0 or 5.0 ng/pulse were administered every 50 min for 24 h beginning on day 10. Administration of 0.5 ng GnRH/pulse for 24 h increased GnRH-R from 35 +/- 3 to 63 +/- 8 fmol/pituitary. There was a clear GnRH dose-related upregulation of GnRH-R to approach nonsuckling levels (140-160 fmol/pituitary) with the 5 ng GnRH dose. At the beginning of GnRH administration, the pituitary was very unresponsive to GnRH. Consistent LH pulses were only observed with 5 ng GnRH/pulse.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of gonadal steroids on gonadotropin secretion in males: studies with perifused rat pituitary cells.

The feedback effects of testosterone (T) and estradiol (E2) on FSH and LH secretion were compared in dispersed pituitary cells from adult male rats perifused with pulses of GnRH. Cells were stimulated with 10 nM GnRH for 2 min every 1 h. T (10 nM) pretreatment for 24 h reduced the amplitude of FSH and LH pulses to 77 +/- 4% (mean +/- SE) and 47 +/- 3% of control values, respectively (P less than 0.01), whereas 6-h T treatment was without effect. By contrast, interpulse secretion of FSH was increased after 24 h T to 184 +/- 7% of the control value (P less than 0.01), but interpulse LH release was unchanged (104 +/- 5%). E2 (0.075 nM) treatment of pituitary cells reduced GnRH-stimulated FSH and LH release within 2 h to 75 +/- 2% and 73 +/- 3% of control values, respectively (P less than 0.01). E2 pretreatment for 24 h stimulated (P less than 0.025) GnRH-induced FSH (136 +/- 10%) and LH (145 +/- 8%) release and also increased (P less than 0.01) interpulse FSH (127 +/- 5%) and LH (145 +/- 8%) secretion. These data indicate that the suppression of FSH and LH secretion by T in males is due in part to a direct effect on the pituitary. The findings that T suppresses GnRH-stimulated FSH less than LH, and that T stimulates interpulse FSH, but not LH, provide evidence for differential regulation of FSH and LH secretion by T. The dissimilar actions of T on GnRH-stimulated pulses and interpulse gonadotropin secretion suggest that interpulse secretion is unrelated to stimulation by GnRH, although its physiological significance is unknown. Since E2, in physiological levels for males, increased pituitary FSH and LH secretion, the suppression of gonadotropin secretion by E2 in vivo in males may result from an effect on the hypothalamic pulse generator; however, additional studies are needed before extending these conclusions to higher mammals and men.

Human follicular gonadotropin releasing peptide analogs. Evaluation of biological (in vitro) and immunological activity.

Human follicular gonadotropin releasing peptide (hF-GRP) has been shown to stimulate pituitary LH and FSH secretion in vitro. Six hF-GRP analogs have been synthesized and evaluated for gonadotropin releasing activity in a rat anterior pituitary primary cell culture system. A tyrosine analog of hF-GRP, [Tyr4]-hF-GRP, retained comparable biological activity in releasing gonadotropins. However, acetylation of hF-GRP in Ac-hF-GRP greatly reduced the in vitro activity. The shorter segments of hF-GRP, hF-GRP-(5-14), and hF-GRP-(10-14), were tested for LH and FSH releasing activity, and it was found that the decapeptide retained moderate activity while the activity of the pentapeptide was markedly lower than hF-GRP. The baboon alpha 1 antitrypsin-(27-40) peptide, b-alpha 1 AT-(27-40), is relatively less potent in releasing LH than hF-GRP. Interestingly, the baboon peptide is more potent (2.5-fold) in releasing FSH under identical conditions. The effect of hF-GRP in releasing LH and FSH was not affected by the presence of LHRH antagonists in cell culture systems. When these peptides were tested for immunological activity in a hF-GRP radioimmunoassay, it was found that hF-GRP and [Tyr4]-hF-GRP have comparable activities. The C-terminal decapeptide of hF-GRP is more active (1.5-fold) in the RIA, and the C-terminal pentapeptide had only one third of the immunoreactivity. The b-alpha 1-AT-(27-40) failed to cross-react in the RIA even at a concentration of 20 micrograms per tube.

Hormonal and Clinical Effects of Ketoconazole in Hirsute Women

The effects of ketoconazole on pituitary-ovarian function and adrenal function were evaluated in nine hirsute women treated with 400-1200 mg/day for 1-6 months. High dose (800-1200 mg/day) ketoconazole treatment decreased serum androstenedione, dehydroepiandrosterone, and testosterone (T) concentrations, while that of 17 alpha-hydroxyprogesterone increased, suggesting a steroidogenic block at the level of 17,20-desmolase. The decreased serum T and increased sex hormone-binding globulin concentrations led to a significant decrease in the free androgen index. Serum estradiol, cortisol, and dehydroepiandrosterone sulfate concentrations did not change. The serum LH concentration and the LH to FSH ratio increased during treatment, suggesting a negative feedback effect of T on pituitary LH secretion. The hormonal changes that occurred during high dose ketoconazole therapy persisted during subsequent low dose (400 mg/day) treatment. The therapeutic effect of ketoconazole on hirsutism manifested itself at 6 months. We conclude that ketoconazole reduces excessive androgen production in a dose-dependent manner and decreases the free androgen index in hirsute women; these changes are accompanied by significant alleviation of hirsutism.

Effects of gonadectomy and hormone replacement on steroid hormone receptors and 5 alpha-reductase activity in pituitaries of male rhesus macaques.

We measured androgen, estrogen, and progestin receptors and 5 alpha-reductase activity in the anterior and posterior pituitary gland of intact and 6-week castrate adult male rhesus monkeys and castrate males which were treated with testosterone (T) or estradiol (E) from time of surgery. Saturation analysis of anterior pituitary tissues from monkeys receiving various treatments revealed an apparent mean dissociation constant (Kd) of 0.53 +/- 0.17 (+/- SE) X 10(-10) mol/L (n = 3) for [3H]R1881 (androgen) binding to cytosol, 2.6 +/- 0.50 X 10(-10) mol/L (n = 3) for [3H]R2858 (estrogen) binding to cytosol, 1.7 X 10(-10) mol/L (n = 2) for [3H]R5020 (progestin) binding to cytosol, and 6.2 X 10(-10) mol/L (n = 2) for [3H )R1881 binding to cell nuclear extract. The highest levels of nuclear androgen receptor (AR) were found in intact males [37.1 +/- 3.5 (+/- SE) fmol/mg DNA; n = 7] and castrated males treated with T for 6 weeks (89.7 +/- 30.2 fmol/mg DNA; n = 5). High levels of nuclear AR corresponded to serum T levels and low serum LH levels. Nuclear AR was undetectable in castrated males and castrated males treated with E. Significantly greater levels of cytosolic AR were detected in intact males (27.5 +/- 1.6 fmol/mg protein) compared to all other groups (P less than 0.05). T or E treatment had no effect on cytosolic AR. Increased levels of cytosolic progestin receptor were found in intact monkeys and after E or T treatment compared to levels in untreated castrates. No differences in 5 alpha-reductase activity were found between any treatment groups. These data indicate that anterior pituitary nuclear androgen receptor is correlated with serum LH levels and support the hypothesis of a direct action of T on anterior pituitary LH secretion. In addition, it appears that cytosolic progestin receptor, but not AR, is regulated by estrogen in intact male rhesus monkeys. In the posterior pituitary, AR dynamics followed a profile in which cytosolic AR increased after castration and decreased after T treatment. Nuclear AR decreased after castration and increased after T treatment. The presence of a dynamic AR system in the posterior pituitary suggests hormonal regulation of its function by androgens.

Social status controls LH secretion and ovulation in female marmoset monkeys (Callithrix jacchus).

The suppression of ovulation in subordinate female marmosets was associated with suppressed pituitary LH secretion and reduced pituitary LH response to gonadotrophin-releasing hormone (GnRH). In subordinate females, basal plasma LH concentrations were commonly below 2 IU/l (n = 5) (maximum 10.7 IU/l). Plasma oestrogen concentrations were similarly low (maximum 0.62 nmol/l) and plasma progesterone concentrations of below 30 nmol/l confirmed the anovulatory condition. This infertility condition was rapidly reversed when subordinate females (n = 5) were removed from their social groups and housed singly, when plasma LH (maximum 140.0 IU/l) and oestrogen (maximum 7.84 nmol/l) concentrations increased preceding ovulation. Infertility was rapidly reimposed when these singly housed females were re-introduced to subordinate status in new social groups, when plasma LH concentrations fell to their previous low values within 4 days; no ovulation occurred thereafter. Plasma oestrogen levels also fell, but less dramatically. The luteal phases of three of the subordinate females were shortened following the re-instatement of subordinate status. The maximum LH response of subordinate females to the highest dose of GnRH (200 ng) was only 19.1 +/- 6.7 IU/l (mean +/- S.E.M.; n = 8): this contrasted with that in dominant females in either the follicular phase (40.0 +/- 13.3 IU/l; n = 6) or the luteal phase (126.7 +/- 24.9 IU/l; n = 10) of the ovarian cycle. These results suggest that the social suppression of fertility in subordinate female marmosets is mediated by impaired hypothalamic GnRH secretion. Such an immediate and precise behavioural control of LH secretion and ovulation is without equal in anthropoid primates.

Hormonal and clinical effects of ketoconazole in hirsute women.

The effects of ketoconazole on pituitary-ovarian function and adrenal function were evaluated in nine hirsute women treated with 400-1200 mg/day for 1-6 months. High dose (800-1200 mg/day) ketoconazole treatment decreased serum androstenedione, dehydroepiandrosterone, and testosterone (T) concentrations, while that of 17 alpha-hydroxyprogesterone increased, suggesting a steroidogenic block at the level of 17,20-desmolase. The decreased serum T and increased sex hormone-binding globulin concentrations led to a significant decrease in the free androgen index. Serum estradiol, cortisol, and dehydroepiandrosterone sulfate concentrations did not change. The serum LH concentration and the LH to FSH ratio increased during treatment, suggesting a negative feedback effect of T on pituitary LH secretion. The hormonal changes that occurred during high dose ketoconazole therapy persisted during subsequent low dose (400 mg/day) treatment. The therapeutic effect of ketoconazole on hirsutism manifested itself at 6 months. We conclude that ketoconazole reduces excessive androgen production in a dose-dependent manner and decreases the free androgen index in hirsute women; these changes are accompanied by significant alleviation of hirsutism.

Differential Regulation of Rat Luteinizing Hormone α- and β-Subunits During the Stimulatory and Down-Regulatory Phases of Gonadotropin-Releasing Hormone Action*

Chronic treatment with agonist analogs of GnRH or long term continuous administration of GnRH results in down-regulation of pituitary LH secretion. We investigated the changes in the LH subunits during the stimulatory and down-regulatory phases of GnRH action in rat pituitary cell monolayer culture. The rat pituitary cells in culture, pretreated with medium alone or GnRH agonist for 48 h, were incubated with graded doses of GnRH for 4 h, and LH, LH alpha, and LH beta concentrations in the media and cell pellets were measured by specific and sensitive RIAs. Cells pretreated with medium alone responded to GnRH with a dose-dependent increase in LH, LH alpha, and LH beta immunoreactivity in the medium. However, rat LH, LH alpha, and LH beta concentrations in the cell pellets showed a dose-dependent decrease with GnRH treatment. Pretreatment with GnRH agonist led to a marked decrease in the LH response of cells to graded doses of GnRH. During this down-regulatory phase, the concentrations of LH beta in the medium remained undetectable even though LH alpha immunoreactivity remained persistently and disproportionately elevated. These data suggest that the alpha- and beta-subunits of rat LH are both coordinately and differentially regulated. During the stimulatory phase of GnRH action, both subunits rise concordantly, but during the down-regulatory phase the secretion of the two subunits becomes unbalanced. The changes in the beta-subunit closely parallel the changes in the concentrations of LH dimer, pointing to the key role of beta-subunit in regulation of LH secretion.

Acute effect of thyroid hormones in mimicking photoperiodically induced release of gonadotropins in Japanese quail

Photoperiodic induction occurs in Japanese quail after exposure to a single long day and this leads to a wave of pituitary LH secretion which lasts for up to 10 days. Pharmacological doses of thyroid hormones mimic this photoperiodic response if given to quail on short days, the magnitude and duration of the rise in LH and FSH output being dose-dependent. Thyroxine (T4) is some 7 times more potent than tri-iodothyronine (T3). There is no effect of T4 on LH secretion in quail already on long days although such birds can increase LH output markedly if treated with Gn-RH. Testosterone prevents the initial rise in LH secretion following T4 but does not block the long-term effect, suggesting that T4 acts high in the photoneuroendocrine chain to mimic long days. The first rise in LH secretion following T4 injection takes place about 24 h after the injection and the time-scale of secretion is quite similar to that seen when quail are exposed to a long day. T4 elicits a rise in LH secretion even if the quail are maintained in darkness. However, T4 does not act simply as ‘light’ for if it is given at the exact time when birds are in a photoinducible state (i.e. 12–16 h after dawn) the rise in LH secretion still occurs 24 h later.

Endogenous opioids modulate the inhibitory effects of androgen on the hypothalamic-pituitary axis of normal women.

This study was designed to investigate the effect of dihydrotestosterone (DHT) on LH secretion in normal women and the role of endogenous opioids in modulating this effect. Pulsatile LH release and maximum LH responsiveness to exogenous GnRH were determined on 3 consecutive days: basally (day 1), during DHT infusion (day 2), and during DHT plus naloxone (Nal) infusion (day 3). Steady state plasma DHT levels of 6.5 +/- 1.1 (+/- SEM) ng/mL (22.5 +/- 3.8 nmol/L) were achieved by infusion. DHT infusion significantly decreased the maximum LH response to GnRH from 35.5 +/- 8.2 to 11.6 +/- 2.8 IU/L (P less than 0.05). This inhibitory effect was not altered by Nal. In addition, DHT significantly decreased LH pulse frequency (basal, 4.3 +/- 0.3; DHT, 2.8 +/- 0.3 pulses/6 h; P less than 0.05), but not the amplitude of the LH pulses. However, after the addition of Nal to DHT, the pulse frequency increased significantly from 2.8 +/- 0.3 to 4.7 +/- 0.3 pulses/6 h (P less than 0.05). The mean plasma LH level did not change during the infusion of DHT alone, but it did increase significantly when Nal was added (DHT, 4.8 +/- 1.0; DHT + Nal, 7.9 +/- 1.0 IU/L; P less than 0.01). The results of this acute pharmacological study suggest that androgens may have two separate effects on the hypothalamic-pituitary axis: 1) inhibition of GnRH release, which appears to be mediated via opioid peptides, and 2) inhibition of pituitary LH secretion, which is not dependent on opioids.

Control of gonadotropin secretion in the ovine fetus: the effects of a specific gonadotropin-releasing hormone antagonist on pulsatile luteinizing hormone secretion.

To demonstrate the dependence of fetal pituitary LH secretion endogenous GnRH, we studied the effects of bolus iv administration of a specific GnRH antagonist analog [GnRH-Ant; (N-acetyl-D-p-chloro-Phe1,2,D-Trp3,D-Arg6,D-Ala10)GnRH] on pulsatile LH release in 10 chronically cannulated ovine fetuses of 104-129 days gestation (term, 147 days). Vehicle alone was given to 13 control fetuses of 107-125 days gestation. Blood samples for LH determination by RIA (NIH LH S16 standard) were taken after injection of either GnRH-Ant (175-300 micrograms dissolved in 1 ml 5% dextrose in water) or vehicle alone for 1.75-5 h. The efficacy of GnRH receptor blockade was then assessed by a bolus iv challenge with 50 micrograms synthetic GnRH. The mean (+/- SEM) observation period per animal was similar for the two groups (3.8 +/- 0.2 h for GnRH-Ant; 3.6 +/- 0.2 h for controls). The frequency of spontaneous pulsatile LH secretion was significantly decreased in the fetuses given GhRH-Ant (2 pulses over 38 h total observation vs. 13 pulses over 47.3 h in control fetuses; P = 0.006). The average interpulse interval was 19.0 h in the GnRH-Ant group compared to 3.6 h in controls. Although the mean pulse amplitude was lower in the GnRH-Ant group (2.8 +/- 1.2 vs. 7.6 +/- 1.1 ng/ml for controls), this difference was not statistically significant (P = 0.065, by one-tailed t test). The mean peak serum LH concentration in response to the GnRH challenge was significantly blunted in the GnRH-Ant group (4.6 +/- 0.8 vs. 20.6 +/- 1.8 ng/ml for controls; P less than 0.001). These results indicate that GnRH-Ant administration causes a virtual cessation of pulsatile LH discharge. As this GnRH-Ant blocks GnRH action at the receptor level, these data demonstrate that pulsatile LH secretion in the ovine fetus is dependent on endogenous GnRH release as early as 104 days gestation.

Effects of vitamin E deficiency on the hormone secretion of the pituitary-gonadal axis of the rat.

Chronological changes of gonadotropin (FSH and LH) and testosterone concentrations in the serum were measured in vitamin E deficient rats to investigate the effects of vitamin E deficiency on the pituitary-gonadal function in rats. The receptor sites and association constant (Ka) for LH and the formation of cyclic AMP in the Leydig cells were also investigated. The results obtained in the present study are as follows: 1) The vitamin E deficient rats showed almost complete hemolysis and extremely increased TBA reacting substances (TBARS) in the serum and liver. 2) The serum LH concentration in the vitamin E deficient group was slightly higher than in the vitamin E supplemented group during the later periods of experiment. 3) The serum FSH concentration in the vitamin E deficient group did not differ significantly from that in vitamin E supplemented group, but became significantly higher than that in the latter at 186 days of experiment. 4) The serum testosterone concentration was always lower in the vitamin E deficient group than in the control. 5) The vitamin E deficient group showed slightly large number of LH/hCG receptor and significantly small Ka (low affinity), as compared with vitamin E supplemented group. The formation of cyclic AMP by Leydig cells decreased significantly in vitamin E deficient group. These results suggest that the vitamin E deficiency exerted a suppressive effect directly on the gonadal function to decrease the hormone synthesis in the Leydig cells and caused the increased secretion of pituitary LH owing to the feedback mechanism.

Ovarian function in ewes treated with antihistamines.

Ewes were treated systemically during the periovulatory period with the antihistamines diphenhydramine (H1-receptor antagonist) and(or) cimetidine (H2-receptor antagonist). None of the treatments prevented ovulation. However, the combination of drugs inhibited subsequent function of the corpus luteum (CL) as assessed by serum measurements of progesterone. Administration of antihistamines did not alter pituitary secretion of LH. Injection of small quantities of diphenhydramine and cimetidine into the antrum of the preovulatory follicle also caused aberrant luteal activity, but no blockade of ovulation. Intrafollicular injection of histamine reversed the inhibitory influence of antihistamines on the CL. Antihistamines suppressed preovulatory thecal edema and antral influx of plasma transudate containing LH. Thus, the effects of antihistamines appear to have been exerted at the follicular level. Function of matured CL was not compromised by peripheral administration of antihistamines. Actions of histamine within the preovulatory ovine follicle do not appear to be a prerequisite for ovulation, but apparently do have an impact on ensuing luteal function. We propose that a hyperemic reaction to histamine in preovulatory follicles enhances vascular filtration of LH. As a consequence, maximal permeation of the avascular granulosal layer of the follicle by LH leads to a normal luteinization response.

Pituitary regulation of corpus luteum progesterone secretion in cyclic rats.

Pituitary LH and PRL secretion during the early postovulatory period of the rat estrous cycle seem to affect the corpus luteum (CL) autonomy to secrete progesterone. Thus, while PRL would act luteotropically, LH would be luteolytic. To further investigate these facts, 4-day cyclic rats, treated with either 1 mg bromocriptine (CB) or 0.25 ml 70% ethanol (ETOH) at 1600 h on estrus, were injected with 0.5 ml of either an anti-LH serum (LHAS) or normal horse serum (NHS) at 0800 h on metestrus. Rats treated at 0800 h on metestrus with both, CB and LHAS, were also used. To verify through a different procedure the effect of LH and/or PRL deprivation in estrous cycle CL progesterone secretion, hypophysectomy (HYPOX) and sham HYPOX (SHAM) were done at 0800 h on metestrus in either CB- or ETOH-injected rats at 1600 h on estrus. Hypophysectomized rats at 1600 h on estrus were also used. Progesterone secretion was prolonged up to 0800 h on diestrus in those rats deprived of LH from 0800 h on metestrus (ETOH/LHAS, -/CB + LHAS, ETOH/HYPOX) compared with controls (ETOH/NHS, ETOH/SHAM). This luteotropic effect was absent in those rats lacking estrous afternoon PRL (CB/LHAS, CB/HYPOX, HYPOX/-). No effect on CL progesterone secretion was detected in those rats exclusively deprived of PRL on the afternoon of estrus (CB/NHS, CB/SHAM). These results suggest that in the absence of the protective effects of PRL secretion on the afternoon of estrus, rat CL become extremely sensitive to the luteolytic effects of early diestrous LH levels, and this results in 4-day estrous cycles.

Involvement of preoptic GABA in generating pulsatile pituitary LH secretion in ovariectomized (ovx) rats treated with GABA-transaminase inhibitors

Involvement of preoptic GABA in generating pulsatile pituitary LH secretion in ovariectomized (ovx) rats treated with GABA-transaminase inhibitors

Effect of an acute injection of melatonin on the basal secretion of hypophyseal hormones in prepubertal and pubertal healthy subjects.

It is well known that the pineal gland can modulate the secretion of pituitary hormones. Melatonin, the main hormone produced by the pineal gland, acts at the hypothalamic site, whereas hypophyseal sensitivity to melatonin seems to change with age. To investigate the influence of pubertal development on the role of the pineal gland in the regulation of the secretion of pituitary hormones, FSH, LH, Prl, TSH and GH responses to melatonin were evaluated in a group of 9 prepubertal and 10 pubertal healthy subjects of both sexes. Melatonin was given im at a dose of 0.2 mg/kg body weight at 3 p.m. Venous blood samples were drawn -20, 0, 20, 40, 60, 90, 120, 180 and 240 min, after melatonin injection. According to the same experimental protocol, venous blood samples were collected during a saline infusion on a separate occasion. FSH, LH, Prl, TSH and GH plasma levels were measured with RIA. In pubertal subjects, a significant rise in the mean Prl levels was seen 90 min after melatonin as compared with those during saline infusion. The Prl melatonin response area was significantly lower in prepubertal treated subjects and significantly higher in pubertal ones compared with the respective controls. The mean GH values showed a significant decrease 120 min after melatonin only in prepubertal subjects; no significant variations were seen in 8 of 10 pubertal subjects, whereas in the last 2 a marked increase was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of estradiol and some antiestrogens (clomiphene, tamoxifen, and hydroxytamoxifen) on luteinizing hormone secretion by rat pituitary cells in culture.

Primary pituitary cell cultures from adult female rats were incubated for 4 or 24 h with various concentrations of estradiol (E2) or the antiestrogens (AE) tamoxifen (TMX), 4-hydroxytamoxifen (OH-TMX), and clomiphene citrate (CC). The luteinizing hormone (LH)-response of these cultures to gonadotrophin releasing hormone (GnRH) was monitored. Treatment for 4 or 24 h with high concentrations (10(-5) M) of the AE significantly decreased the GnRH-induced LH-release by the gonadotrophs. The negative E2-effect, which is observed in this model after 4 h was enhanced and the positive E2-effect, which occurs after 24 h, was completely reversed into a negative effect by these high AE-concentrations. Treatment of pituitary cells with increasing concentrations of E2 (10(-13)-10(-6) M) or AE (10(-12)-10(-5) M) for 24 h led first to a dose dependent increase of the LH-response to 5 X 10(-10) M GnRH. At higher E2- or AE-concentrations this positive effect was lost, resulting in bell shaped dose-response curves. The following maximal effective concentrations (EDmax) were found: E2 = 10(-10) M, OH-TMX = 10(-9) M, CC = 10(-7) M, TMX = 10(-6) M. Incubation of pituitary cells for 24 h with concentrations of AE near their EDmax and stimulation with increasing concentrations (10(-11)-10(-7) M) of GnRH resulted in significant increases of LH-secretion over a wide range of GnRH-concentrations. It is concluded that AE possess marked intrinsic activities on pituitary LH-secretion: at extremely high concentrations they suppress the GnRH-induced release of the gonadotrophin. At lower concentrations they increase the pituitary LH-response to GnRH in a manner which is qualitatively indistinguishable from that of E2.

Preoptic gaba release inregulation of pituitary LH secretion in ovariectomized (OVX) rats treated with GABA transaminase inhibitors and in ovariectomized estrogen-primed (OVX-E2B) rats

Preoptic gaba release inregulation of pituitary LH secretion in ovariectomized (OVX) rats treated with GABA transaminase inhibitors and in ovariectomized estrogen-primed (OVX-E2B) rats

Short-term pituitary desensitization to LH-RH after pulsatile LH-RH in the ovariectomized rat: an in vivo experiment.

The development of acute insensitivity of pituitary LH secretion to LH-RH after a short exposure to LH-RH is described. In the first experiment, ovariectomized (OVX), phenobarbital-pretreated rats were given pulses of LH-RH (1.25 or 6.25 ng/100 g body weight (b.w.), intravenously). In rats given 1.25 ng at time 0, 6.25 ng at 60 min, 1.25 ng at 80 min and 1.25 ng at 120 min, there was a substantial increase in plasma LH after the first two injections, no increase after the third injection and a relatively small increase after the fourth one. In other rats treated identically but not given a 1.25-ng dose at 80 min, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after the 1.25-ng dose given at time 0. If the 1.25-ng LH-RH pulses given at times 0 and 80 min were replaced by a rat pituitary extract, the plasma LH rise in response to the 1.25-ng dose at 120 min was comparable to that seen after administration of pituitary extract. In the second experiment, OVX phenobarbital-pretreated rats were given 1.25 ng LH-RH/100 g b.w. at t = 0. They were then divided into three groups, each receiving 1.25, 3.75 or 6.25 ng LH-RH/100 g b.w. at t = 60 min. Each of these three groups was again divided into three groups which received 1.25 ng LH-RH/100 g b.w. at 80, 100 or 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of gonadectomy and steroid treatment on plasma gonadotropins and the response of superfused pituitaries to gonadotropin-releasing hormone in the turtle Sternotherus odoratus

Gonadectomized (gonadex) turtles, Sternotherus odoratus, had significantly elevated plasma FSH, but LH was less consistently affected. Estradiol (E 2)-implants suppressed plasma FSH in gonadex females but not in males; testosterone (T) partially suppressed FSH in males. In contrast, E 2-treatment markedly suppressed pituitary LH content and in vitro LH secretion in gonadex and intact turles (inhibitory effects of E 2 were less in intact than ovariectomized females). These steroid effects were relatively specific for gonadotropin; pituitary TSH content was not altered. In vitro, pituitary LH secretion responded to doses of GnRH ≥ 1 ng/ml and LH output remained elevated for at least 3 hr of continuous superfusion with gonadotropin-releasing hormone (GnRH). In general, gonadectomy elevated pituitary responsiveness to GnRH while E 2 and T suppressed this responsiveness; the effects of E 2 are greater in gonadectomized than intact turtles. Thus, negative gonadal feed-back appears to be involved in the secretion of gonadotropins in turtles, and steroidal actions may be partly due to suppression of pituitary hormone content and responsiveness to GnRH.