Effect of dopamine on gonadotropin-releasing hormone-induced gonadotropin secretion in postmenopausal women

Five healthy women who had previously undergone spontaneous menopause and had not received exogenous estrogens were studied with infusions of synthetic GnRH and dopamine to ascertain the site of dopaminergic modulation of pituitary gonadotropin secretion. Infusion of dopamine at 4 micrograms/kg . min for 5 h induced a significant decrease in circulating LH concentrations, but not those of FSH. LH levels returned to baseline concentrations during the postinfusion period. Infusion with synthetic GnRH at 10 micrograms/h for 5 h induced a biphasic change in circulating gonadotropin levels. When dopamine and GnRH were simultaneously infused for 5 h, FSH and LH responses were not statistically different from those observed when GnRH was infused alone. We conclude that in normal postmenopausal women, dopamine modulates pituitary gonadotropin secretion by affecting GnRH-secreting neurons in the median eminence and possibly at other hypothalamic sites.     

Pharmacodynamics of gonadotropin-releasing hormone. 1. Effects of gonadotropin-releasing hormone pulse contour on pituitary luteinizing hormone secretion in vivo in sheep

The gonadotropin-releasing hormone (GnRH) waveform arrives at the pituitary gonadotropes via the pituitary portal blood and provides the immediate suprapituitary stimulus to luteinizing hormone (LH) secretion. Despite their importance, nature and influence of the physiological GnRH waveform in vivo have been difficult to study. Recent pharmacological and in vitro studies have suggested the potential importance of the wave contour as a specific and independent factor in the pharmacodynamic effects of GnRH on pituitary gonadotrope LH secretion in vivo, and it has been hypothesized that the steepness of the rising edge of the GnRH wave contour is a specific determinant of pituitary LH secretion. In order to investigate the pharmacodynamic influence of GnRH pulse wave contour on pituitary LH secretion in vivo, variations in plasma LH responses to alterations in GnRH wave contour were measured in chronic ovariectomized, hypothalamopituitary-disconnected sheep undergoing physiological pulsatile GnRH maintenance regimen at a fixed dose (250 ng/pulse) and frequency (interpulse interval 120 min). Variable wave contours were then generated by administration of the same total GnRH pulse dose over various lengths of time from near-instantaneous bolus to increasing lengths of constant-rate infusion time up to 8 min. This model allowed specific examination of pulse wave contour in the absence of concurrent changes in endogenous GnRH or sex steroid secretion and holding constant GnRH pulse dose, frequency, and route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of neuropeptide Y on the in vitro release of gonadotropin-releasing hormone, luteinizing hormone, and beta-endorphin and pituitary responsiveness to gonadotropin-releasing hormone in female macaques

The objectives of these studies were to examine the release of gonadotropin-releasing hormone (GnRH) and beta-endorphin-like activity (beta-EP) from macaque hypothalami, and the release of luteinizing hormone (LH) and GnRH-induced LH from macaque anterior pituitaries in response to neuropeptide Y (NPY) treatment. Anterior hypothalamic (AH) and mediobasal hypothalamic (MBH) blocks of tissues and the adenohypophysis were bisected along the midline into two equal-sized fragments. Fragments were superfused with medium for 3 h, followed by 3 h of either NPY (80 nM) or medium alone. In a separate experiment, adenohypophyseal (AP) fragments were superfused in accordance with the same protocol (3 h medium - 3 h NPY or medium) except that exogenous GnRH (352 nM) was added for 30 min at the beginning of hour 3 and again at the beginning of hour 6. Immunoactive GnRH, beta-EP, and LH levels were measured in superfusate samples (400 microliters) collected at 10-min intervals. GnRH levels rose within 20-30 min of initiation of NPY treatment, and elevated GnRH release was sustained for the duration of NPY exposure of both AH and MBH fragments from ovarian intact (INT) rhesus (Macaca mulatta: n = 8; p less than 0.05) or Japanese (Macaca fascicularis; n = 4; p less than 0.01) macaques. NPY treatment had no effect on either AH or MBH fragments isolated from ovariectomized (OVX) rhesus macaques (n = 4 for AH, and n = 5 for MBH). In AP fragments isolated from INT rhesus macaques (n = 8), NPY stimulated LH release within 1 h of treatment (p less than 0.05), whereas NPY had no effect on pituitaries from OVX animals (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence that norepinephrine and epinephrine systems mediate the stimulatory effects of ovarian hormones on luteinizing hormone and luteinizing hormone-releasing hormone

Results from previous investigations have suggested an important role for central epinephrine (EPI) systems in mediating the stimulatory effects of ovarian hormones on LH release in ovariectomized female rats. The purpose of these experiments was 1) to test whether selective inhibition of EPI synthesis blocks the sequential accumulation and decline of LHRH concentrations in the median eminence that precedes the ovarian hormone-induced LH surge and 2) to test whether the stimulatory ovarian hormone regimen enhances the activity of EPI systems in the hypothalamus. Ovariectomized rats were treated with estradiol, followed 2 days later by progesterone. Animals were treated before progesterone administration with saline, one of the EPI synthesis inhibitors [SK&F 64139 (2,3-dichloro-tetrahydroisoquinoline HCl) or LY 78335 (dichloro-alpha-methylbenzylamine)], or the dopamine-beta-hydroxylase inhibitor FLA-63 (bis-4-methyl-1-homopiperazinyl thiocarbonyl disulfide), which inhibits NE and EPI synthesis. The catecholamine synthesis inhibitors blocked or delayed the afternoon LH surge. FLA-63 completely prevented the accumulation of LHRH in the median eminence that preceded the rise in LH release. However, selective EPI synthesis inhibition with SK&F 64139 only partially prevented this increase in LHRH. A second EPI synthesis inhibitor, LY 78335, delayed both the LH surge and the rise in LHRH. In a second experiment, the administration of estradiol and progesterone to ovariectomized rats increased the alpha-methyltyrosine-induced depletion of hypothalamic EPI, suggesting increased activity in this system during the LH surge. Further experiments localized this effect to the medial basal hypothalamus. The depletion of both NE and EPI after synthesis inhibition was also enhanced during an earlier period, approximating the time of LHRH accumulation. These results suggest that the ovarian hormones activate both NE and EPI systems to stimulate the early afternoon rise of LHRH in the median eminence and to induce the subsequent LH surge.     

Differential suppression of follicle-stimulating hormone and luteinizing hormone secretion in vivo by a gonadotropin-releasing hormone antagonist

Because of some indication that FSH secretion is less dependent than LH secretion on GnRH in vivo, we performed experiments to examine the effects of a GnRH antagonist (antag) on LH and FSH secretion. We first showed that pituitary cells superfused with GnRH showed a similar pattern of suppressed secretion of both LH and FSH in response to addition of antag. In contrast, antag administration to ovariectomized rats had differing effects on LH and FSH secretion. Serum LH was suppressed in a dose-dependent fashion by 2 h (20-50% of control values). Recovery from the lower doses of antag was seen by 12 h, but the two highest doses maintained serum LH levels at 10% of control values for 72 h. In contrast, the effect on serum FSH was not manifested until 12 h. FSH was maximally decreased only to 40-60% of control values. The two highest doses maintained this effect for 72 h. These results reinforce previous suggestions that FSH secretion in vivo may occur independently of acute changes in GnRH secretion, and may have an GnRH-independent component.     

The actions of serotonin, norepinephrine, and epinephrine on hypothalamic processes leading to adenohypophyseal luteinizing hormone release

The effects of third ventricle (3V) infusion of exogenous monoamines on the secretion of LH were investigated in Nembutal-blocked proestrous rats after electrochemical stimulation (ECS) of the medial preoptic area (MPOA). Two microcannulae were anatomically oriented through the ventral surface of the brain to establish a push-pull flow system in the 3V at the rate of 3.9 microliter/min for 160 min. Serotonin perfusions (2.6 x 10(-3) M for 160 min at 3.9 microgram/min) significantly depressed the MPOA-ECS-induced rise in plasma LH at 160 and 200 min, but did not diminish the secretion of LH after an intraatrial injection of 250 ng LRH. Seemingly, the reduced plasma LH which follows MPOA-ECS in serotonin-treated rats is the consequence of decreased hypothalamic LRH secretion. Desipramine (3.6 x 10(-4) M), a norepinephrine (NE) uptake inhibitor, did not prevent serotonin inhibition. In contrast, the specific serotonin uptake inhibitor. Lilly 110140 (3.2 X 10(-4) M), and cyproheptadine (2.9 x 10(-4) M) blocked the inhibitory effects of serotonin. Serotonin was also tested in proestrous rats anesthetized with Nembutal within 1 h after the beginning of the light cycle (morning rats) and in proestrous rats at least 15 min after the start of the dark cycle (night rats). Serotonin (2.6 x 10(-3) M) failed to diminish the rise in plasma LH after ECS in morning rats, but depressed the ECS-induced increase of LH in night rats. Perfusions of 3 X 10(-8) M NE at 3.9 microliter/min for 160 min augmented the plasma LH increase after MPOA-ECS but only at 160 and 200 min, while its response to LRH was not tested. At higher concentrations, 3 x 10(-6) M NE markedly suppressed the rise in plasma LH after ECS and also depressed the secretion of LH after an intraatrial injection of LRH. In contrast, 3 x 10(-6) M epinephrine which inhibited the response to LRH, potentiated the MPOA-ECS-induced rise in plasma LH. Higher concentrations of epinephrine (3 x 10(-4) M), however, inhibited both the ECS and LRH-induced secretion of LH.     

Effects of glucocorticoids on responsiveness of luteinizing hormone and follicle-stimulating hormone to gonadotropin-releasing hormone by male rat pituitary cells in vitro

To determine if the inhibitory effects of glucocorticoids on GnRH-stimulated secretion of LH observed in male rats in vivo are exerted directly on the pituitary, dispersed pituitary cells from adult male rats were treated with 60 or 600 ng/ml cortisol (F) or corticosterone (B) during one or two 48-h incubations. Control cells received no glucocorticoids. During the second 48 h, some cells from each group were treated with GnRH (2.4 X 10(-11)-6.2 X 10(-8) M). Concentrations of LH and FSH in media and cells were measured by RIA. Treatment with steroids had no effect on basal secretion or maximal GnRH-stimulated secretion of LH, or on maximal secretion of FSH. Treatment with 600 ng/ml B for 96 h increased basal secretion of FSH relative to controls. All treatments with glucocorticoids increased the slopes of the GnRH dose-response curves for both LH and FSH, cell content of LH, total (cells + medium) LH, and total FSH. Incubation with 6 micrograms/ml F or B or 60 ng/ml dexamethasone gave similar results. Decreasing the time period of the second incubation to 6 h results in no significant differences between control cells and cells treated with B or F. These results show that glucocorticoids have different effects in vivo and in vitro, suggesting that inhibitory effects of glucocorticoids on secretion of LH in vivo may not be exerted directly on the pituitary but are exerted elsewhere, perhaps by altered hypothalamic secretion of GnRH. Also, these results show that male and female pituitaries in vitro respond differently to glucocorticoids.     

Estrogen regulates the gonadotropin-releasing hormone-stimulated secretion of biologically active luteinizing hormone

Estrogen produces time-dependent bidirectional effects on the GnRH-stimulated release of immunoactive LH in various species. To examine estrogen's regulation of biologically active LH secretion in response to pulsatile stimulation by GnRH, we studied estrogen-deficient postmenopausal women basally and during treatment with diethlystilbesterol (DES; 1 mg, orally, daily). Basal and GnRH-stimulated plasma concentrations of bioactive LH were assayed by the in vitro rat interstitial cell testosterone bioassay. GnRH-promoted LH secretory bursts in response to two consecutive stimuli were quantitated by multiple parameter deconvolution analysis. Basal half-lives of LH averaged 171 +/- 17 min (immunoactive) and 223 +/- 10 min (bioactive). Analysis of variance revealed a significant decrease in mean basal plasma bioactive LH concentrations on days 10 and 30 of DES treatment. Mean serum immunoactive LH concentrations fell similarly. DES significantly increased the half-life of immunoactive LH (days 5 and 10), but did not change that of bioactive LH. GnRH self-priming of bioactive LH secretion (increased LH secretory peak 2 compared to peak 1) was demonstrated, with a maximal value on day 10 of DES treatment. In addition, the ratio of the mass of bioactive to immunoactive LH secreted in response to the first GnRH pulse was significantly enhanced by estrogen on day 5, whereas that after the second pulse of GnRH was significantly suppressed on day 30 of DES. The self-priming action of GnRH on bioactive LH release evident in the presence of oral DES was corroborated in a separate group of six women, who were treated for 30 days with 17 beta-estradiol via an intravaginally placed Silastic ring. In conclusion, we infer that estrogen exerts a highly selective effect on the gonadotroph secretory process, such that successive GnRH stimuli result in an increase in the maximal rate and mass of secretion of biologically active LH.     

Biphasic effects of estrogen on gonadotropin-releasing hormone-induced luteinizing hormone release in monolayer cultures of rat and monkey pituitary cells

The negative feedback effect of estrogen on LH secretion has been difficult to demonstrate in monolayer cultures of rat pituitary cells. The purpose of the present study was to establish the experimental conditions required for manifestation of this response and, in the process, to develop models for investigating the actions of steroids on pituitary cells. Both dynamic and static incubation systems were used. For perifusion experiments, trypsin-dispersed pituitary cells from rats at random stages of the estrous cycle were attached to glass coverslips with poly-L-lysine, incubated for 48 h, and then mounted in Sykes-Moore chambers. In each of these experiments, two chambers were perifused concurrently: one with medium containing 1.8 X 10(-10) M 17 beta-estradiol and the other with medium alone. GnRH (4.2 X 10(-9) M) was coinfused for 5 min out of every hour, and samples of perifusate were collected as 5-min fractions for assay of LH. Estrogen treatment significantly (P less than 0.01) suppressed LH release in response to the first five GnRH pulses compared to the control value. The inhibition was most pronounced early in the perifusion, but had disappeared by 6 h. These results demonstrate that estradiol exerts a potent but transient inhibition of GnRH-induced LH release in monolayer cultures of rat pituitary cells. In a subsequent set of experiments, we modified a static incubation system to assess sequentially the biphasic effects of estrogen on LH release by the same group of cells. Cultures of rat pituitary cells that had been established 42 h previously were treated simultaneously for 3 h with 17 beta-estradiol (3.7 X 10(-10) M) and various concentrations of GnRH (5 X 10(-10) to 1 X 10(-7) M) to measure the inhibitory effects of the steroid on LH secretion. This experiment was repeated on the same cells after 27 h of steroid exposure to estimate the facilitory actions of estrogen on LH release. The negative feedback of estrogen was demonstrable in static cultures of rat pituitaries provided that the period of estrogen exposure and duration of incubation were brief. Moreover, the results indicate that the same groups of cells can be used on consecutive days to investigate the inhibitory and stimulatory effects of estrogen on LH secretion. Experiments with cultures of monkey pituitary cells yielded similar results. Taken together, these findings indicate that cultured pituitary cells are responsive to the biphasic actions of estradiol and demonstrate the utility of two model systems for investigating these phenomena.     

Prostaglandins mediate the endotoxin-induced suppression of pulsatile gonadotropin-releasing hormone and luteinizing hormone secretion in the ewe

Five experiments were conducted to test the hypothesis that PGs mediate the endotoxin-induced inhibition of pulsatile GnRH and LH secretion in the ewe. Our approach was to test whether the PG synthesis inhibitor, flurbiprofen, could reverse the inhibitory effects of endotoxin on pulsatile LH and GnRH secretion in ovariectomized ewes. Exp 1-4 were cross-over experiments in which ewes received either flurbiprofen or vehicle 2 weeks apart. Jugular blood samples were taken for LH analysis throughout a 9-h experimental period. Depending on the specific purpose of the experiment, flurbiprofen or vehicle was administered after 3.5 h, followed by endotoxin, vehicle, or ovarian steroids (estradiol plus progesterone) at 4 h. In Exp 1, flurbiprofen reversed the endotoxin-induced suppression of mean serum LH concentrations and the elevation of body temperature. In Exp 2, flurbiprofen prevented the endotoxin-induced inhibition of pulsatile LH secretion and stimulation of fever, reduced the stimulation of plasma cortisol and progesterone, but did not affect the rise in circulating tumor necrosis factor-alpha. In Exp 3, flurbiprofen in the absence of endotoxin had no effect on pulsatile LH secretion. In Exp 4, flurbiprofen failed to prevent suppression of pulsatile LH secretion induced by luteal phase levels of the ovarian steroids progesterone and estradiol, which produce a nonimmune suppression of gonadotropin secretion. In Exp 5, flurbiprofen prevented the endotoxin-induced inhibition of pulsatile GnRH release into pituitary portal blood. Our finding that this PG synthesis inhibitor reverses the inhibitory effect of endotoxin leads to the conclusion that PGs mediate the suppressive effects of this immune/inflammatory challenge on pulsatile GnRH and LH secretion.     

The effects of age on the postreceptor regulation of luteinizing hormone secretion by gonadotropin-releasing hormone.

We studied the effects of age on the roles of phosphoinositide (PI) and protein kinase C (PKC) in luteinizing hormone (LH) release by gonadotropin-releasing hormone from mouse pituitaries. Pituitary cells from intact and 14-day ovariectomized (OVX) mice aged 4-8 months, 10-12 months and 14-18 months were cultured at a dilution of 3 x 10(5) cells/ml of M199-bovine serum albumin medium for 3 days prior to stimulation with either buserelin or phorbol ester (phorbol myristate acetate, PMA), while LH was assayed by radioimmunoassay using anti-rat LH antibody (NIDDK-5-10). In intact young mice, buserelin and PMA specifically induced time- and dose-dependent increases in LH release with specific mean ED50 of 0.82 x 10(-11) M (buserelin) and of 1.6 x 10(-8) M (PMA) and a maximal LH release of 138 +/- 15 ng/10(6) cells after a 3 h stimulation period. Age did not affect the ED50 of either agonist but significantly reduced their ability to release LH. This reduction was more pronounced for buserelin than for PMA and was evident as early as middle-age. OVX resulted in a significant increase in both basal and stimulated LH release, but did not affect the age-related reduced secretion rate of LH by either agonist. Buserelin stimulated the incorporation of [3H]inositol into [3H]inositol phosphates (IP) in a dose-dependent manner, which was unaffected by either age or OVX. We conclude that, with aging, there occurs a reduced LH release rate to both buserelin and PKC stimulations, uncoupled to changes in PI-IP cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of glucocorticoids on secretion of luteinizing hormone and follicle-stimulating hormone by female rat pituitary cells in vitro

To determine if the divergent effects of glucocorticoids on the circulating levels of LH and FSH in female rats are exerted directly on the pituitary, adult female pituitary cells were treated either with no glucocorticoids or with 60 or 600 ng/ml cortisol or corticosterone during one or two 48-h incubations. During the second 48 h, some cells from each group were treated with GnRH (1.7 X 10(-12) - 4.6 X 10(-9) M). Concentrations of LH and FSH in media and cells were measured by RIA. Basal secretion of LH was inhibited 38-43% by different glucocorticoid treatment during the first 48 h and 21% by 600 ng/ml corticosterone during the second 48 h. In contrast, basal secretion of FSH was enhanced 22-64% during the first 48 h and 25-124% during the second 48 h. Secretion of LH in response to maximal stimulation with GnRH was unaffected by glucocorticoids, but maximal secretion of FSH was increased 68%. The responsiveness of the cells to GnRH, as determined from the slope of the GnRH dose-response curve for LH, was increased 43-50% by cortisol. The slope of the dose-response curve for FSH was unaffected, but the mean concentration of FSH as a function of the log dose of GnRH was increased 45-79%. Glucocorticoids had no effect on cell content of LH or total LH per dish, either under basal or maximal GnRH-stimulated conditions. Glucocorticoids increased basal cell content of FSH 41-82%, basal total FSH 35-93%, and maximal GnRH-stimulated total FSH 40-84%. These results suggest that the only negative effect of glucocorticoids on reproduction exerted at the level of the pituitary is a slight suppression of basal LH secretion, that glucocorticoids affect the pituitary directly by increasing FSH synthesis, and that the divergent effects of glucocorticoids on LH and FSH provide a novel model for differential regulation of the gonadotropins.     

Calcium dependence of the inhibitory effect of gonadotropin-releasing hormone on luteinizing hormone-induced cyclic AMP production in rat granulosa cells

The role of calcium in the inhibitory action of the GnRH superagonist, [D-Ala6]des-Gly10-GnRH N-ethylamide (GnRHa), on LH-stimulated cAMP production was studied in cultured granulosa cells obtained from immature hypophysectomized diethylstilbestrol (DES)-implanted rats. After culture for 48 h with FSH to induce LH receptors, cells were incubated for 2 h with LH or LH plus GnRHa. In this system, the cAMP response to LH was independent of extracellular calcium. In the presence of 0.25 to 1 mM extracellular calcium, 10(-8) M GnRHa caused a 15 to 40% inhibition of LH-stimulated cAMP production. Omission of extracellular calcium completely abolished the inhibitory effect of GnRHa upon LH-induced cAMP production. The inhibitory effects of GnRHa on prostaglandin E2 (PGE2) and isoproterenol-induced cAMP productions were also markedly reduced in the absence of extracellular calcium. Addition of the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX), reversed the inhibitory action of GnRHa on LH-induced cAMP production. These results demonstrate that extracellular calcium is necessary for the acute inhibitory action of GnRHa upon LH-induced cAMP production in cultured rat granulosa cells, and indicate that increased degradation of cAMP may be a contributing factor for this effect of GnRHa.     

Biosynthesis, glycosylation, and secretion of rat luteinizing hormone alpha- and beta-subunits: differential effects of orchiectomy and gonadotropin-releasing hormone

We have studied the de novo biosynthesis and secretion of LH subunits in pituitary quarters from orchiectomized and intact control adult male rats and their regulation by GnRH. After labeling with [35S]cystine ([35S]Cys), [35S]methionine, or [3H]glucosamine ([3H]GlcN) in the presence or absence of 10(-8) M GnRH, tissue lysates and media were immunoprecipitated with antisera to LH beta, then LH alpha (after removal of TSH by immunoprecipitation with anti-TSH beta), and the products were analyzed by sodium dodecyl sulfate gradient gel electrophoresis. During a 12-min pulse labeling with [35S]methionine, three forms of immunoreactive alpha were labeled at 21,000, 18,000, and 12,000 mol wt. After a 30-min chase with excess unlabeled methionine, the 12,000 form decreased from 10% to 3% of total radioactivity, while the 21,000 form increased from 57% to 69%, implying a precursor-product relationship. Neither orchiectomy nor GnRH had any effect on [35S]Cys or [3H]GlcN incorporation into intracellular or secreted total proteins. After a 6-h continuous labeling, incorporation of [35S]Cys into intracellular combined LH alpha in castrates was 158% of the control value, combined LH beta was 304%, and free alpha was 466%. The [3H]GlcN to [35S]Cys ratio, reflecting relative glycosylation, was unchanged in castrates for total proteins or LH alpha and somewhat decreased for LH beta and free alpha. Orchiectomy increased [35S]Cys-labeled secreted LH beta and free alpha to 183% and 231% of control values, respectively. Relative glycosylation of secreted LH alpha, LH beta, and free alpha was unchanged in castrates. Incorporation of [35S]Cys into intracellular combined LH alpha, LH beta and free alpha-subunit was unaffected by GnRH in pituitaries from intact rats. In castrates, LH alpha was unchanged, but LH beta and free alpha were slightly increased. Incorporation of [3H]GlcN into intracellular combined LH alpha, LH beta, and free alpha was increased with GnRH in both intacts and castrates, such that the 3H to 35S ratio, reflecting relative glycosylation, was also increased with GnRH. In castrates, the ratios, as a percentage of the control, were, respectively 250%, 250%, and 223% for LH alpha, LH beta, and free alpha. In intact animals, the ratios were 221%, 281%, and 143%, respectively. Incorporation of both [35S]Cys and [3H]GlcN into secreted subunits was increased in most instances, such that the 3H to 35S ratio was increased only for LH beta.(ABSTRACT TRUNCATED AT 400 WORDS)     

Interactions among epinephrine, thyrotropin (TSH)-releasing hormone, dopamine, and somatostatin in the control of TSH secretion in vitro

Epinephrine and TRH independently release TSH from rat anterior pituitary cells in primary monolayer culture (ED50, 11 and 5 nM, respectively; maximum responses, 80% and 110%, respectively). The effects of these compounds together are additive, even at concentrations at which each is maximally effective alone. Dopamine inhibited basal and epinephrine-stimulated TSH secretion by 25 +/- 5% (+/-SE; ED50, 50 +/- 9 nM in each case). Somatostatin was effective against epinephrine-stimulated, but not basal, TSH secretion (80 +/- 4% inhibition; ED50, 1 +/- 3 nM). The data show that epinephrine is a potential regulator of TSH secretion by its own action and via its interactions with TRH, dopamine, and somatostatin.     

Examination of the effects of epinephrine, norepinephrine, and dopamine on aldosterone production in bovine glomerulosa cells in vitro

This study was undertaken to explore the possibility that the neurogenic amines epinephrine and norepinephrine may influence aldosterone production in vitro and to examine again the previously reported inhibitory effect of dopamine on aldosterone production. This was accomplished using bovine glomerulosa cell suspensions and a highly specific RIA for aldosterone. Epinephrine and norepinephrine (10(-6) - 10(-10) M) had no significant effect on aldosterone production. Both basal and angiotensin II-stimulated aldosterone production were significantly inhibited by dopamine, 10(-4) M, P less than 0.05. Basal aldosterone production was unaffected by lower concentrations of dopamine whereas angiotensin II-stimulated aldosterone production was inhibited in a dose-dependent manner that was significant to 10(-6) M dopamine (P less than 0.05). Pretreatment of glomerulosa cells with the dopamine antagonist metoclopramide impaired the inhibitory effect of dopamine on aldosterone production. This study supports the hypothesis that dopamine may be a significant inhibitor of aldosterone production in vivo. The other neurogenic amines studied, epinephrine and norepinephrine, had no significant effect on aldosterone production in vitro.     

Spontaneous, gonadotropin-releasing hormone-induced, and progesterone-inhibited pulsatile secretion of human chorionic gonadotropin in the first trimester placenta in vitro

Using a multichannel superfusion apparatus, the secretion of human chorionic gonadotropin (hCG) was measured at 1-6 minute intervals in placental explants at 7-9 weeks of gestation. hCG was found to be secreted in distinct pulses (4-5 fold above baseline) every 11-23 minutes peak to peak. Addition of one minute pulses of GnRH analog significantly increased, whereas pulses of progesterone decreased, pulsatile hCG secretion.