Effects of interleukin-1 beta on secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by cultured rat anterior pituitary cells

Interleukin-1 beta (IL-1 beta) at doses of 0.15 and 1.5 nM significantly inhibited FSH secretion and stimulated LH secretion by cultured rat pituitary cells after 24-72 hr incubation whereas 15 pM of IL-1 beta was not effective. Treatment with IL-1 beta for 12-48 hr did not affect intracellular content of FSH. However, treatment with 0.15 and 1.5 nM of IL-1 beta for 72 hr significantly suppressed intracellular content of FSH whereas various doses of IL-1 beta incubated with the cells for 12-72 hr showed no effect on the intracellular content of LH. Pretreatment with IL-1 beta for 48 hr inhibited both GnRH-mediated LH and FSH secretions by the pituitary. The secretion of FSH and LH mediated by an activator of protein kinase C, phorbol 12-myristate 13-acetate, was also significantly suppressed by pretreatment with IL-1 beta for 48 hr. These results suggest that (a) IL-1 beta has opposite effects on the secretion of LH and FSH and (b) pretreatment with IL-1 beta suppresses GnRH-mediated stimulation of LH and FSH by the pituitary and this suppressive effect of IL-1 beta may involve the suppression of a protein kinase C-dependent mechanism.     

Stimulatory and inhibitory effects of progesterone on FSH secretion by the anterior pituitary.

The purpose of this study was to investigate whether progesterone exerted progesterone receptor mediated direct effects on the anterior pituitary in the secretion of FSH and whether such effects were mediated through the 5 alpha-reduction of progesterone. Treatment of anterior pituitary dispersed cells for 48 h with 0.5 nM estradiol reduced the ED50 for gonadotropin releasing hormone (GnRH)-stimulated FSH release from 0.58 to 0.36 ng/ml and the ED50 for GnRH-induced LH release from 0.54 to 0.19 ng/ml. When dispersed pituitary cells were treated with 0.5 nM estradiol and exposed to various doses of progesterone for 1 to 6 h, the most consistent rise in basal and GnRH-stimulated FSH release was observed with the 50 nM dose of progesterone with a 3-h exposure period. All three doses of progesterone elevated basal LH and GnRH-stimulated LH was increased by the 50 and 100 nM doses of progesterone during the 3-h period of treatment. Using the 50 nM dose of progesterone, basal and GnRH-stimulated LH was increased after 2, 3 and 6 h of progesterone treatment. When the period of exposure of progesterone was extended to 12, 36 or 48 h, there was a significant inhibition of GnRH-stimulated FSH release. GnRH-stimulated LH release was inhibited at 36 and 48 but not 12 h after progesterone treatment. These studies showed that the effect of progesterone administered for periods of 1 to 6 h enhanced the secretion of LH and FSH whereas progesterone administered for periods beyond 12 h inhibited FSH and LH release by dispersed pituitary cells in culture. These results are similar to those observed in vivo after progesterone treatment. Furthermore estrogen priming of the dispersed pituitary cells was necessary to observe the effects of progesterone. The progesterone antagonist RU486 prevented the progesterone-induced rise in GnRH-stimulated FSH release. Furthermore the 5 alpha-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane- 17 beta-carboxamide also prevented the progesterone-induced rise in GnRH-stimulated FSH release in estrogen-treated dispersed pituitary cells. These results indicate that the anterior pituitary is a major site of action of progesterone in the release of FSH and that 5 alpha-reduction of progesterone plays an important role in FSH release.     

Prolactin release and milk removal induced by suckling and milking in lactating ewes is prevented by L-dopa treatment

The effect of L-DOPA on milk removal and on prolactin release during suckling or milking was studied in lactating ewes. Various doses of L-DOPA (25, 50, 100 and 200 mg per animal) were injected iv 30 min before the suckling or milking period. Control ewes were injected with 0.9% NaCl solution only. Milking induced a significant long-lasting release of prolactin. An inhibition of milk removal was obtained with the dose of 200 mg of L-DOPA. An inhibition of prolactin secretion was observed related to the dose of drug administered. The inhibitory effect of 200 mg of L-DOPA on the secretion of prolactin after milking lasted for about 120 min, and thereafter a significant increase in serum prolactin level occurred. This increase in serum prolactin was not due to a "rebound" effect of L-DOPA, since the milking stimulus had to be present to induce the delayed increase in prolactin. Doses of 25 or 50 mg of L-DOPA prevented the surge of prolactin observed immediately after milking, but a long-lasting release of prolactin was obtained thereafter. The inhibitory effect of L-DOPA on prolactin release could be overridden by the suckling or milking stimuli according to the dose administered. The suckling stimulus was more effective than milking in overriding the inhibitory effect of the low dose of L-DOPA. The results indicate that milk removal and prolactin release induced by milking or suckling in lactating ewes is inhibited by an increase in monoamines at the hypothalamic-hypophyseal level.     

The rapid effects of luteinizing hormone releasing hormone agonists and antagonists on the mouse pituitary in vitro

The effect of luteinizing hormone releasing hormone (LHRH) and its analogs on the release of FSH and LH by 20 day old whole mouse pituitary incubated in vitro for 3-4 hrs was investigated. Three agonistic analogs (AY 25650, 25205 and Buserelin) all of which are reported to be superactive in vivo showed approximately the same potency in this in vitro test system. Preincubation of the pituitaries for 1 h with the antagonistic analogs [Ac Dp Cl Phe1,2, D Trp3, D Phe6, D Ala10] LHRH and [Ac Dp Cl Phe1,2, D Trp3, D Arg6, D Ala10] LHRH inhibited the secretion of LH and FSH induced by 2.5 x 10(-9)M LHRH. The inhibitory response was dose dependent. The continued presence of the antagonists was not required for effective suppression of the LHRH effect. Experiments designed to find out the minimum time required for eliciting suppression of LHRH revealed that preincubation of the pituitary with the second antagonist for 5 mins followed by removal was adequate to produce effective inhibition of gonadotropin release. At lower doses of the antagonist, LH release was more effectively inhibited than FSH release. The results suggest that antagonistic analogs can effectively bind to LHRH receptors in the whole pituitary incubation preventing the subsequent action of LHRH. With the present incubation system assessment of bioactive LH and FSH release is possible within 24 hrs.     

Regulation of pulsatile gonadotropin secretion by estrogen, inhibin, and follistatin (activin-binding protein) in ovariectomized rats.

The following study was conducted to examine the effects of estrogen and polypeptides, given either alone or in combination, on pulsatile gonadotropin secretion. One week after ovariectomy, rats received s.c. injections of oil or various doses (0.5, 5, 20 micrograms) of estradiol benzoate (EB) followed 1 day later by i.v. administration of 60 micrograms purified porcine follistatin, 10 micrograms recombinant inhibin, or the appropriate vehicle. Four hours after injection of the nonsteroids, blood was collected at 10-min intervals for 2 h, and the effects on pulsatile hormone release were assessed. Administration of EB alone dose-dependently suppressed mean and trough (lowest point between two pulses) FSH levels and all parameters of pulsatile LH release. Both follistatin and inhibin at the doses employed suppressed mean FSH levels to an equivalent extent (40%). Follistatin, but not inhibin, suppressed FSH pulse amplitude, while neither polypeptide alone influenced FSH pulse frequency or any parameter of pulsatile LH release. The effects of follistatin and EB on mean FSH levels were additive at all EB doses, whereas the effects of inhibin and EB were additive only at the middle EB dose. Follistatin in combination with the lowest EB dose significantly suppressed mean LH levels. These studies are the first to demonstrate that combined treatment with estrogen and the nonsteroids follistatin and inhibin is more efficacious in suppressing FSH release than treatment with either agent alone, thereby indicating that both steroids and nonsteroids are probably important in the physiological regulation of FSH secretion in rats. The additive effects of these compounds on FSH secretion could form the basis for exploring novel contraceptive interventions.     

Predominant involvement of mu-rather than delta- or kappa-opiate receptors in LH secretion

Opiate alkaloids and opioid peptides have been shown to suppress plasma LH and FSH levels via a naloxone sensitive mechanism in several species including man. Three subtypes of opiate receptors have been characterized: mu, delta and kappa. The present study was designed to investigate their role in gonadotropin release. Three highly selective opioid ligands, DAGO, MRZ and DTE12 (a dimeric tetrapeptide enkephalin), were injected intraventricularly into chronically ovariectomized rats. Injection of the mu-agonist at doses of 1 and 10 nmol produced a significant suppression of LH secretion, while the delta- and kappa-agonists had no significant effect. Thus, the mu-receptor seems to be the primary opiate receptor involved in the regulation of LH secretion. None of the opiate agonists employed had an effect on FSH secretion.     

The modes of the anterior hypothalamic area as the regulatory center for the gonadotropin release

The effects of the anterior hypothalamic area (AHA) implants of gonadal steroid estrogen and progesterone as well as the effects of electrical stimulation and electrolytic lesion confined in this area on the gonadotropin secretion were investigated in ovariectomized estradiol (20 microgram sc)-primed adult Wistar rats housed in light and temperature controlled room. Progesterone implants evoked the rise of serum LH by 6 hr whereas estradiol implants suppressed serum FSH by 24 hr after implantation. Electrical stimulation effectively depleted both gonadotropins with a latency not shorter than 6 hr. The lesion significantly prevented FSH elevation investigated at 72 hr post ovariectomy and potentiated FSH secretion in response to estradiol treatment at 3 week post ovariectomy. The result revealed the involvment of the AHA in LH release mechanism which required progesterone activation while its involvement in FSH regulatory mechanism depended upon estrogen. The area was elucidated as the inhibitory as well as the stimulatory loci for the feedback action of estrogen on FSH release.     

The L-DOPA-sparing effect of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP] in reserpine-pretreated rats

R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP], a highly potent enhancer of impulse propagation-mediated release of catecholamines and serotonin in the brain, and significantly increased the locomotor activity of normal rats at the doses of 0.3 and 1 mg/kg s.c. (P < 0.05), while L-DOPA (200 and 400 mg/kg i.p.) had no significant effect. The locomotor activity of rats simultaneously administered L-DOPA and (-)-BPAP was significantly higher than with (-)-BPAP alone (P < 0.05). In rats pretreated with reserpine (1 mg/kg i.v.), the hypolocomotion was significantly reversed by 400 mg/kg i.p. L-DOPA, or 1 or 3 mg/kg s.c. (-)-BPAP (P < 0.05). Furthermore, the combined administration of subthreshold doses of 200 mg/kg i.p. L-DOPA and 0.3 mg/kg s.c. (-)-BPAP highly potentiated the locomotor activity in the reserpine-pretreated rats. However, (-)-BPAP failed to reverse the hypolocomotion in rats pretreated with reserpine + alpha-methyl-DL-p-tyrosine. Thus, (-)-BPAP was demonstrated to possess the L-DOPA-sparing effect in normal and reserpine-pretreated rats.     

Effect of steroids in combination with LH-RH on the release of LH and FSH in LH-RH-primed immature male rat.

LH and FSH release of immature male rats was remarkedably enhanced by LH-RH if primed with LH-RH one hour before. The effect of exogenous steroids on the action of the second LH-RH was investigated. C-18, C-19 and C-21 steroids in different doses were tested. Blood samples were collected from the jugular vein immediately before and 30 min after the second LH-RH injection. Serum LH and FSH were determined by respective radioimmunoassays. The concomitant increase of LH and FSH was not induced by all the steroids administered iv. Estrone or 17alpha-hydroxyprogesterone suppressed LH and FSH release. Estradiol-17beta preferentially suppressed LH release. Cortisone, progesterone or dehydroepiandrosterone significantly facilitated FSH release, whiel 20alpha-dihydroprogesterone or 20beta-dihydroprogesterone selectively promoted LH release. The sc injection of most steroids dissolved in oil tended to augment the acute release of LH but not FSH. 20alpha-Dihydroprogesterone was particularly potent in this concern. Dehydroepiandrosterone or androstenedione was effective in maintaining FSH release for a longer period. These data revealed that potentiated LH and FSH release induced by the second LH-RH was readily modified by steroids administered simultaneously.     

A nongenomic action of estradiol as the mechanism underlying the acute suppression of secretion of luteinizing hormone in ovariectomized ewes

The objective of the present study was to determine how rapidly estradiol (E2) was able to suppress the secretion of LH in ovariectomized (OVX) ewes and to evaluate the ability of conjugated forms of E2 (E2 conjugated to BSA [1,3,5(10)-estratrien-3,17beta-diol-6-one-6-carboxymethyloxime:BSA [E2-BSA] and a novel conjugate, E2 conjugated to a small peptide [E2-PEP]) to mimic the actions of E2 on secretion of LH and FSH. Animals (n = 5-6 per group) were given infusions for 4 h of 50 microg of E2 or equimolar concentrations of E2-BSA or E2-PEP. Treatments with E2, E2-BSA, and E2-PEP each induced an acute suppression of LH secretion (<20 min, P < 0.01). In contrast, E2, but not E2-BSA or E2-PEP, induced the characteristic preovulatory-like surge of LH (at 10 h after priming treatment) and decreased secretion of FSH (at 4 h after priming treatment). In conclusion, the acute inhibition of LH secretion induced by E2 in OVX ewes supports the concept of a nongenomic action as the mechanism underlying the sudden suppression in secretion of LH. In addition, the fact that conjugated forms of E2 mimicked only the acute suppression of secretion of LH, without inducing the putative genomic actions on secretion of LH or FSH (i.e., a preovulatory-like surge), suggests that the acute effect of E2 may be mediated via the plasma membrane.     

Extracellular Concentrations of Dopamine and Metabolites in the Rat Caudate After Oral Administration of a Novel Catechol-O-Methyltransferase Inhibitor Ro 40–7592

The effect of the systemic administration of a novel, orally active, catechol-O-methyltransferase (COMT) inhibitor, Ro 40-7592, on the in vivo extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was studied by transcerebral microdialysis in the dorsal caudate of freely moving rats. Ro 40-7592 (at doses of 3.0, 7.5, and 30 mg/kg p.o.) elicited a marked and long-lasting reduction of HVA, and at doses of 7.5 and 30 mg/kg, an increase of DOPAC output, but it failed to increase DA output. The administration of L-beta-3,4-dihydroxyphenylalanine (L-DOPA, 20 and 50 mg/kg p.o.) with a DOPA decarboxylase inhibitor (benserazide) increased both HVA and DOPAC output, but failed to modify significantly extracellular DA concentrations in dialysates; in contrast, combined administration of L-DOPA+benserazide with Ro 40-7592 (30 mg/kg p.o.) resulted in a significant increase in DA output. Ro 40-7592 prevented the L-DOPA-induced increase in HVA output and markedly potentiated the increase in DOPAC output. To investigate to what extent the increase in extracellular DA concentrations was related to an exocitotic release, tetrodotoxin (TTX) sensitivity was tested. Addition of TTX to Ringer, although abolishing DA output in the absence of L-DOPA, partially reduced it in the presence of L-DOPA+Ro 40-7592 and even more so after L-DOPA without the COMT inhibitor. The results of the present study suggest that metabolism through COMT regulates extracellular concentrations of DA formed from exogenously administered L-DOPA but not of endogenous DA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of castration and estradiol treatment on the postovulatory secretion of follicle-stimulating hormone in the mated rabbit

The effects of castration on the postovulatory secretion of follicle-stimulating hormone (FSH) was measured in mated rabbits. When ovaries were removed at 12 or 18 h postcoitum, FSH increased within 24 h of surgery but without evidence of the previously observed pattern of FSH secretion in the postovulatory period. To prevent the postcastration rise in FSH, various doses of estradiol were injected into does castrated 12 h after mating. Two micrograms estradiol/kg, given daily, was found to prevent the postcastration rise of FSH but was not sufficient to suppress the postovulatory secretion of FSH in intact animals. The postovulatory pattern of FSH release was disrupted in does castrated at either 12 or 18 h postcoitum despite adequate estradiol replacement therapy. Furthermore, in chronically castrated does treated with estradiol (2 micrograms/kg per day), neither mating nor human chorionic gonadotropin (hCG) injection elicited any change in blood FSH levels even though both treatments have been previously found to cause a postovulatory FSH surge. The results of these studies indicate that the ovary, by way of some ovarian secretion, is required for the postovulatory secretion of FSH in the rabbit. The necessary ovarian factor does not appear to be estradiol.     

Pharmacological study of cholinergic mechanisms of compensatory ovarian hypertrophy in rats.

Treatment of hemicastrated adult female rats with nicotine increased the compensatory ovarian hypertrophy (COH) while central n-cholinolytic IEM-506 decreased COH and prevented the estrogen-induced suppression of COH. Administration of L-DOPA abolished the effect of IEM-506, and disulfiram blocked gonadotropic action of nicotine. Elevation of the dose of arecoline decreased COH and the sensitivity of hypothalamo-gonadotropic complex to estrogen suppression. Treatment of rats with L-DOPA and disulfiram abolished the late effect of arecoline. Central m-cholinolytic metamizyl decreased COH, potentiated the effect of estrogen and prevented the gonadotropic effect of L-DOPA. The regulatory role of m-cholinergic systems in noradrenaline mediation of gonadotropic function and n-cholinergic system in dopamine ones are suggested.     

The effect of cyclic nucleotides on secretin secretion in canine duodenal mucosa in vitro

We examined the effects of cyclic nucleotides and calcium on secretin release from canine duodenal mucosal explants incubated in organ culture media. Time course studies revealed that at pH 7.4, 5 and 10 mM dibutyryl cyclic adenosine monophosphate (DBcAMP) increased secretin release progressively, reaching a peak at 2 hours. Two mM of DBcAMP at pH 7.4 did not increase secretin release but at pH 4.5, all 3 doses potentiated secretin release. DBcAMP-stimulated secretin release was not dependent on the influx of extracellular calcium. Graded doses of 3-isobutyl-1-methylxanthine (IBMX) did not stimulate secretin secretion but 1 mM IBMX with 2 mM DBcAMP increased secretin secretion significantly. Dibutyryl cyclic guanosine monophosphate, cholera toxin and 5'-guanylyl-imidodiphosphate (GPP(NH)p) did not stimulate basal secretion release. The release of secretin from our explants incubated at pH 7.4 was not due to specific leakage because all of our viability studies revealed that our explants were functionally intact at the end of 2 hours. Our observations suggest that cyclic nucleotides may participate in the intracellular regulation of secretin secretion.     

The inhibitory action of corticotropin-releasing hormone on gonadotropin secretion in the ovariectomized rhesus monkey is not mediated by adrenocorticotropic hormone

Earlier observations in our laboratory indicated that i.v. infusion of human/rat corticotropin-releasing hormone (hCRH) suppresses pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in ovariectomized rhesus monkeys. Since cortisol secretion increased significantly as well, it was not possible to exclude the possibility that this inhibitory effect of hCRH on gonadotropins was related to the activation of the pituitary/adrenal axis. The purpose of the present study was to determine the role of pituitary/adrenal activation in the effect of hCRH on LH and FSH secretion. We compared the effects of 5-h i.v. infusions of hCRH (100 micrograms/h, n = 7) and of human adrenocorticotropic hormone (ACTH) (1-24) (5 micrograms/h, n = 3; 10 micrograms/h, n = 3, 20 micrograms/h, n = 3) to ovariectomized monkeys on LH, FSH, and cortisol secretion. As expected, during the 5-h ACTH infusions, cortisol levels increased by 176-215% of baseline control, an increase similar to that observed after CRH infusion (184%). However, in contrast to the inhibitory effect observed during the CRH infusion, LH and FSH continued to be released in a pulsatile fashion during the ACTH infusions, and no decreases in gonadotropin secretion were observed. The results indicated that increases in ACTH and cortisol did not affect LH and FSH secretion and allowed us to conclude that the rapid inhibitory effect of CRH on LH and FSH pulsatile release was not mediated by activation of the pituitary/adrenal axis.     

Pituitary regulation of preovulatory estrogen secretion in the rat

The factors stimulating estrogen secretion in the preovulatory phase and an attempt to explain the mechanism of termination of estrogen secretion are discussed. Female Wistar rats, hypophysectomized at 1 p.m. in proestrus, were injected with rat pituitary extracts. Ovarian venous blood was collected and the estrogen activity of the plasma was measured. The estrogen secretion was minimized within 3 hours after hypophysectomy. The rat pituitary extract caused an 11-fold increase of estrogen concentration in the ovarian venous blood within 1 hour. Either LH or FSH alone was able to restore the estrogen secretion: LH took 1 hour to reach maximal response, FSH 2 hours. In the 1-hour test, the minimal effective dose for LH appeared to be less than .25 mcg per rat, for FSH, 2.5 mcg per rat. The total ability of the two preparations to produce estrogen appeared to be the same. 10 I.U. of prolactin slightly stimulated estrogen secretion, but 20 mU of ACTH was quite negative. These results demonstrate the pituitary gonadotropin dependency of estrogen secretion from the ovary having ripened follicles. It also showed that the ovary, after completion of ovulatory surge of LH, abolished its reactivity to the pituitary extract containing sufficient amount of substances in promoting estrogen secretion. Either LH or FSH was able to terminate estrogen secretion even at minute doses as small as 10 mcg. This shows that both FSH and LH provide a dual effect on ovarian estrogen secretion at the preovulatory stage, promotion and suppression. Promotion is an acute and direct action of hormones on steroidogenesis and suppression probably a delayed and indirect action of ovulation-inducing hormone, the release of which initiates the differentiation of estrogen-forming cells towards ovulation unfavorable to estrogen synthesis.     

Median eminence lesions reveal separate hypothalamic control of pulsatile follicle-stimulating hormone and luteinizing hormone release

The effects of hypothalamic lesions designed to destroy either the anterior median eminence (ME) or the posterior and mid-ME on pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined in castrated male rats. In sham-operated animals, mean plasma FSH concentrations rose to peak at 10 min after the onset of sampling, whereas LH declined to a nadir during this time. In the final sample at 120 min, the mean FSH concentrations peaked as LH decreased to its minimal value. In rats with anterior ME lesions, there was suppression of LH pulses with continuing FSH pulses in 12 of 21 rats. On the other hand, in animals with posterior to mid-ME lesions, 3 out of 21 rats had elimination of FSH pulses, whereas LH pulses were maintained. Fifteen of 42 operated rats had complete ME lesions, and pulses of both hormones were abolished. The remaining 12 rats had partial ME lesions that produced a partial block of the release of both hormones. The results support the concept of separate hypothalamic control of FSH and LH release with the axons of the putative FSH-releasing factor (FSHRF) neuronal system terminating primarily in the mid- to caudal ME, whereas those of the LHRH neuronal system terminate in the anterior and mid-median eminence. We hypothesize that pulses of FSH alone are mediated by release of the FSHRF into the hypophyseal portal vessels, whereas those of LH alone are mediated by LHRH. Pulses of both gonadotropins simultaneously may be mediated by pulses of both releasing hormones simultaneously. Alternatively, relatively large pulses of LHRH alone may account for simultaneous pulses of both gonadotropins since LHRH has intrinsic FSH-releasing activity.     

Selective release of follicle-stimulating hormone and luteinizing hormone by 5 alpha-dihydroprogesterone and 3 alpha, 5 alpha-tetrahydroprogesterone in pregnant mare's serum gonadotropin-primed immature rats exposed to constant light

The effects of 5 alpha-dihydroprogesterone (5 alpha-DHP) and 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alpha-THP) on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release were examined in the pregnant mare's serum gonadotropin (PMSG)-primed immature female rat (8 IU PMSG at 28 days of age) maintained in constant light. Control rats kept in 14L:10D conditions exhibited proestrous-like surges of LH and FSH release with peak levels attained at 1800 h on the second day after PMSG treatment. In rats exposed to constant light, the PMSG-induced surges of LH and FSH were not only delayed until 1000 h on the third day after PMSG, resulting in a delay in ovulation, but were also significantly attenuated when compared to the gonadotropin surges that occurred on Day 2 in rats kept under normal light-dark conditions. The administration of 5 alpha-DHP significantly enhanced the release of FSH at 1000 h on Day 3 when compared to constant light-exposed controls, but had no effect on LH. Treatment with 3 alpha, 5 alpha-THP selectively potentiated the release of LH at 1000 h on Day 3 and had an attenuating effect on FSH release on Days 2 and 3. These observations confirm earlier findings in the immature ovariectomized estrogen-primed rat and suggest that 5 alpha-DHP and 3 alpha, 5 alpha-THP may have significant roles in the regulation of FSH and LH secretion.     

Modification of mouse islet function by 5-hydroxytryptamine, dopamine and their precursors

5-Hydroxytryptamine (5-HT) and dopamine were found to inhibit glucose-induced insulin release and 45Ca2+ net uptake in islets microdissected from ob/ob-mice. Dopamine was more potent than 5-HT. L-DOPA, the precursor of dopamine, had an effect similar to that of dopamine and this effect was reduced by benserazide. L-5-hydroxytryptophan, the precursor of 5-HT, potentiated glucose-induced insulin release and stimulated 45Ca2+ uptake. This effect was also blocked by benserazide. It is concluded that dopamine is a stronger inhibitor than 5-HT and that the different actions of 5-HTP and L-DOPA might be explained by this difference in the magnitude of inhibition.