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1.
Suppressive effects of ethanol (ETOH) on in vivo serum growth hormone (GH) levels have been reported in both humans and animals. To determine whether this effect could be mediated directly at the pituitary level, we have designed a series of in vitro experiments utilizing pituitary cells from ETOH naive animals maintained in monolayer culture. We report that ETOH, in doses ranging from 50 to 400 mg%, caused a prompt and sustained reduction in basal GH secretion, as well as a significant fall in intracellular GH content. These data establish that the in vivo effects of ETOH on GH can be accounted for, at least in part, by a direct effect at the pituitary level, possibly due to reduced GH synthesis.  相似文献   

2.
The effects of oestradiol-17beta, testosterone and progesterone alone and together with cycloheximide on the basal and gonadotrophin releasing hormone (Gn-RH)-induced release of gonadotrophins were studied in cultured dispersed rat pituitary cells. In the control group (no steroid treatment), GnRH significantly stimulated the release of LH and FSH; cycloheximide partially inhibited this response, although it had no effect on the basal secretion of gonadotrophins. A dose of 5 ng oestradiol/ml had no significant effect on the response to GnRH; at a dose of 100 ng/ml the GnRH-induced release of LH was significantly augmented whereas the release of FSH was inhibited. Cycloheximide blocked the augmenting effect of oestradiol. The basal release of LH was slightly but significantly inhibited in response to 10 ng testosterone/ml and increased in response to progesterone (200 ng/ml). Testosterone at both dose levels and progesterone significantly inhibited the GnRH-induced release of LH and FSH and in testosterone and progesterone-treated groups, the response to GnRH was inhibited by cycloheximide, but not beyond the levels observed in the control group. It is concluded that steroids can act directly on the pituitary cells, that oestradiol stimulates the GnRH-induced release of LH and that cycloheximide blocks this stimulatory effect. Testosterone and progesterone, on the other hand, partially inhibit the response to GnRH.  相似文献   

3.
Exogenous cyclic adenosine nucleotides increase gonadotrophin-releasing hormone (GnRH) receptors in intact cultured rat pituitary cells in a similar manner to that observed with GnRH itself. In this study the calcium and microtubule dependency of GnRH receptor up-regulation was examined in vitro. Treatment of pituitary cells in Ca2+ and serum-containing media with either GnRH (1 nmol/l), K+ (58 mmol/l) or dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) for 7-10 h routinely resulted in a 50-100% increase in GnRH receptors. Incubation of pituitary cells with the calcium channel blocker verapamil, for 7 h, or the calcium chelator EGTA, for 10 h, had no effect on basal receptor levels but prevented the increase in GnRH receptors stimulated by either GnRH, K+ or dbcAMP. Luteinizing hormone release measured with the same stimulators over a 3-h period was prevented by both verapamil and EGTA. Calcium ionophore (A23187) increased GnRH receptors by 40-60% at low concentrations (10 and 100 nmol/l) while higher concentrations (10 and 100 mumol/l) reduced receptor levels. Luteinizing hormone release was not increased by receptor-stimulating concentrations of A23187, but was by higher concentrations (10 mumol/l). None of these pretreatments, for up to 10 h, impaired the subsequent LH response of the cells to increasing doses of GnRH. Vinblastine (1 mumol/l did not affect basal receptor levels but markedly reduced the increase in GnRH receptors stimulated by GnRH, K+ and dbcAMP. This concentration of vinblastine had no effect on LH release.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

4.
The characteristics and dynamics of hormone secretion in vivo and in vitro were investigated in six patients with gonadotropin-secreting pituitary adenomas. All six tumors secreted and contained FSH and different combinations of LH, beta-LH, and alpha-subunit. In addition, immunohistochemical examination of the pituitary tumor tissue showed staining with both LH and FSH in three and either LH or FSH in the other three tumors. TRH and GnRH stimulated hormone secretion in vivo and in vitro, and they also increased the hormone content of the cultured tumor cells. Bromocriptine significantly inhibited hormone release and reduced the hormone content of the tumor cells. In vivo, 2.5 mg bromocriptine significantly suppressed plasma hormone levels; the inhibiting effect on alpha-subunit concentrations was in general more marked than that on LH and FSH. We conclude that hormone release by gonadotropin-secreting pituitary adenomas can be stimulated by TRH and GnRH and inhibited by bromocriptine. Most of these tumors synthesize FSH, but there is a wide variation in the production of LH, beta-LH, and alpha-subunits. The sensitivity of hormone release to bromocriptine suggests that chronic therapy with this drug might have a beneficial effect on pituitary tumor size.  相似文献   

5.
The effects of atrial natriuretic factors (ANFs) on anterior pituitary hormone secretion and cyclic nucleotide production were investigated in cultured rat pituitary cells. ANF had no effect on ACTH, GH, PRL, and TSH release or on cAMP production either on basal hormone levels or during stimulation of their secretion by the appropriate releasing factor. However, ANF markedly stimulated cGMP production in both mixed anterior pituitary cells and enriched anterior pituitary cell populations fractionated by centrifugal elutriation. Unexpectedly, certain ANF preparations, Bachem rat ANF-(5-28) and rat ANF-(5-25), markedly stimulated LH release from cultured anterior pituitary cells and gonadotroph-enriched elutriated pituitary cells. The same ANFs also displaced [125I-D-Lys6]GnRH ethylamide from binding to anterior pituitary membranes with potencies similar to their LH-releasing activities. Immunoprecipitation of ANF with a specific antiserum abolished the effect of ANF on cGMP production, but did not change the effect of ANF on LH release. In conclusion, ANF did not affect anterior pituitary hormone secretion or cAMP production, but stimulated cGMP formation. The effect of certain ANF preparations on LH release appears to be attributable to peptide contamination with a potent GnRH agonist.  相似文献   

6.
Z Naor  A M Leifer  K J Catt 《Endocrinology》1980,107(5):1438-1445
The effects of gonadotropin-releasing hormone (GnRH) on cGMP production and LH release in cultured rat pituitary cells are markedly dependent upon the extracellular calcium concentration. The absence of calcium from incubation media caused almost complete loss of the GnRH effects on cGMP production and LH release but did not change the stimulation of cAMP accumulation by GnRH in the pituitary of the adult male rat. In female rat pituitary cells, reduction of the extracellular calcium concentration increased the concentration of GnRH required to produce half-maximal LH release and decreased the maximal gonadotropin output but had no significant effect on basal LH release. The divalent cation ionophore A23187 stimulated LH release, and this action was dependent on extracellular calcium. Both GnRH and A23187 were found to have maximal effects when the calcium concentration was 0.6 mM, and their actions were not additive. The calcium antagonists, verapamil and lanthanum, caused concentration-dependent inhibition of the actions of GnRH, with half-maximal blockade values of 10(-5) and 3 X 10(-6) M, respectively, and had no effect on basal LH release. The binding of a radioiodinated GnRH analog, [D-Ser(t-Bu)6]des-Gly10-GnRH-N-ethylamide, to pituitary GnRH receptors was unchanged in the absence of extracellular calcium. These observations demonstrate that stimulation of pituitary cGMP production and LH release by GnRH is dependent on extracellular calcium. The site at which calcium is required during GnRH action is at a postreceptor locus before cGMP formation.  相似文献   

7.
OBJECTIVE: Leptin is an adipocyte-derived hormone, which is the product of the obese gene and it is thought to play important roles in pubertal development and maintenance of reproductive function in the female. In a study using adult male or female rats, it was found that leptin stimulated the secretion of gonadotropin directly from the pituitary in a dose-related manner. However, there is no study in juvenile female rats before puberty. METHODS: In this study, we cultured pituitary cells from 4-, 6- and 8-week-old female Wistar rats with leptin (0-10(-7)mol/l) and gonadotropin-releasing hormone (GnRH) (0 or 10(-8) mol/l). Basal or GnRH-stimulated secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and their synthesis within cells were determined by radioimmunoassay (RIA). RESULTS: Leptin induced bell-shaped dose--response curves of basal LH and FSH secretion from cultured cells of every age-group of rats studied. The most effective concentration of leptin on the basal secretion of LH and FSH from 6- and 8-week-old cultured pituitary cells was 10(-10) mol/l. This leptin concentration was consistent with circulating physiological serum leptin levels at each age. As for juvenile 4-week-old pituitary cells, the most effective concentration was 10(-11) mol/l which was lower than that of 6- and 8-week-old rats. It was consistent with the circulating serum leptin levels of 4-week-old rats. Also, the synthesis and the GnRH-stimulated secretion of LH and FSH were effectively controlled by leptin at concentrations similar to the serum leptin levels of given ages. CONCLUSIONS: Leptin induced pituitary cells to synthesize and secrete both LH and FSH regardless of the presence or absence of GnRH. The concentration of leptin that induced the greatest synthesis and secretion of gonadotropins from pituitary cells changed around the pubertal period. The most effective leptin concentrations in each experiment were similar to the physiological serum leptin level at each animal age. These results indicate that leptin stimulates gonadotrophs not only in the pubertal and the mature period but also in the juvenile period before puberty. It is also conceivable that leptin may modulate the sensitivity of gonadotrophs until the appearance of GnRH stimulation, and may be the factor that brings about puberty onset.  相似文献   

8.
It has been established that kisspeptin regulates reproduction via stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion, which then induces pituitary luteinizing hormone (LH) release. Kisspeptin also directly stimulates pituitary hormone release in some mammals. However, in goldfish, whether kisspeptin directly affects pituitary hormone release is controversial. In this study, synthetic goldfish kisspeptin-1((1-10)) (gKiss1) enhances LH and growth hormone (GH) release from primary cultures of goldfish pituitary cells in column perifusion. gKiss1 stimulation of LH and GH secretion were still manifested in the presence of the two native goldfish GnRHs, salmon (s)GnRH (goldfish GnRH-3) and chicken (c)GnRH-II (goldfish GnRH-2), but were attenuated by two voltage-sensitive calcium channel blockers, verapamil and nifedipine. gKiss-induced increases in intracellular Ca(2+) in Fura-2AM pre-loaded goldfish pars distalis cells were also inhibited by nifedipine. These results indicate that, in goldfish, (1) direct gKiss1 actions on pituitary LH and GH secretion exist, (2) these actions are independent of GnRH and (3) they involve Ca(2+) signalling.  相似文献   

9.
Inositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate, administered exogenously at a concentration of 3 x 10(-5) mol/l increased LH release in superfused rat pituitary cells by 950 +/- 267% and 281 +/- 83%, respectively. This stimulatory effect was reversible and dose-dependent. Other inositol phosphates (inositol 1-monophosphate, inositol 1,4,5,6-tetrakisphosphate, inositol 1,3,4,5,6-pentakisphosphate and inositol 1,2,3,4,5,6-hexakisphosphate), tested in vitro, did not significantly influence LH release. In saponin-permeabilized cells, the rate of basal and stimulated LH release was twice that in non-permeabilized cells. Penetration of inositol bisphosphate and inositol trisphosphate into saponin-treated pituitary cells did not increase the secretory potency of these agents compared with their effect on non-permeabilized cells. The new findings document that inositol trisphosphate formation occurs within 5-45 s after GnRH (10(-7) mol/l) administration and seems to be involved in mediating the rapid, first phase of LH release, whereas inositol bisphosphate formation occurs after 3-15 min and is probably related to later phases of LH secretion. Our results suggest that inositol bisphosphate and inositol trisphosphate are important regulators of the release of luteinizing hormone and can exert their effects not only intracellularly, but also extracellularly.  相似文献   

10.
M S Smith 《Endocrinology》1982,110(3):882-891
The ability of pituitaries from lactating animals to secrete LH and FSH in response to gonadotropin-releasing hormone (GnRH) was studied in vitro using a pituitary incubation system. Hemipituitaries were exposed to GnRH for 6 min during each hour of incubation. LH release by anterior pituitaries (APs) from day 5 postpartum rats nursing eight pups, in response to pulsatile exposure to GnRH, was significantly less than that released by APs from diestrous cycling females. Even though the amount of LH released by APs increased as lactation progressed, LH release by APs from day 15 postpartum rats nursing eight pups was still less than LH release by APs from diestrous females. In contrast pituitaries from lactating females nursing two pups released amounts of LH similar to that released by pituitaries from diestrous females, whereas females deprived of their litters for 48 h showed a greater response than diestrous females. Generally, there was a good quantitative relationship between the amount of LH released in vitro and plasma LH concentrations for all the intact groups studied. The ability of lactation to suppress the postcastration rise in serum LH also was demonstrated in vitro as pituitaries from ovariectomized or intact females nursing eight pups released similar amounts of LH on days 5 and 10 postpartum. However, by day 15 postpartum, even though serum LH concentrations were still very low, pituitaries from ovariectomized lactating females released LH in vitro at a rate similar to pituitaries from nonlactating rats. Serum FSH concentrations were not suppressed but similar in intact and cycling females. Also, the total amount of FSH released in vitro in response to GnRH by pituitaries from lactating and cycling females did not differ significantly, even though LH release differed greatly among these groups of animals. However, the patterns of GnRH-stimulating FSH secretion differed among intact lactating, ovariectomized lactating, and nonlactating females. Pituitary LH concentrations were similar on day 5 postpartum and diestrus and on day 15 postpartum and proestrus. Pituitary FSH concentrations on day 5 postpartum were similar to those during diestrus and proestrus and had increased 2-3 times by day 15 postpartum. Generally, there was no correlation between the amount of LH or FSH released by pituitaries in response to GnRH and pituitary gonadotropin content. In summary, the inability of pituitaries from lactating rats to respond adequately to large doses of GnRH in vitro suggests that the suckling stimulus indirectly suppresses pituitary responsiveness to GnRH. This suppression differentially affects basal LH secretion, but not basal FSH secretion, and may be the direct result of inadequate GnRH stimulation in vivo.  相似文献   

11.
Neurohypophysial hormones have been implicated in the control of anterior pituitary function, and oxytocin has been shown to stimulate gonadotrophin excretion and ovarian follicular development in certain species. To determine the role of neurohypophysial peptides in the control of gonadotrophin release, their actions on LH and FSH secretion were analysed in rats in vivo and in vitro. In adult female rats, administration of oxytocin during early pro-oestrus advanced the spontaneous LH surge and markedly increased peripheral LH levels at 15.00 h compared with control animals. In cultured pituitary cells from adult female rats, oxytocin and vasopressin elicited dose-related increases in LH and FSH release. Such responses were not affected by a potent gonadotrophin-releasing hormone (GnRH) antagonist that abolished GnRH agonist-induced release of LH and FSH. Oxytocin did not enhance GnRH agonist-stimulated gonadotrophin release to the same extent as it increased basal secretion, but at low concentrations of GnRH agonist the effects were additive. The gonadotrophin responses to oxytocin and vasopressin were inhibited by the specific neurohypophysial hormone antagonists, [d(CH2)5D-Ile2,Ile4,Arg8]vasopressin and [d(CH2)5Tyr (Me),Arg8]vasopressin. These results provide direct evidence that neurohypophysial hormones can stimulate gonadotrophin secretion through a receptor system distinct from the GnRH receptor. Such a mechanism could represent a complementary hypothalamic control system for long-term modulation of LH and FSH secretion by exerting a basal or tonic influence on gonadotrophin production.  相似文献   

12.
The secretory response of pituitary gonadotropes to stimulation by gonadotropin-releasing hormone (GnRH) has been extensively studied, but the mechanism by which GnRH evokes gonadotropin synthesis and release has not been clarified. In particular, there has been conflicting evidence about the role of cAMP in GnRH-induced release of LH. To examine this question in more detail, the actions of GnRH on LH release and cAMP production were analyzed in primary cultures of collagenase-dispersed rat pituitary cells. In this system, addition of 10(-10)--10(-6) M GnRh to cultured pituicytes caused rapid release of LH into the incubation medium. In contrast, GnRH caused no significant change in intracellular or extracellular cAMP or in occupancy by cAMP of the regulatory subunit of protein kinse. Neither dibutyryl cAMP nor methyl isobutylxanthine (MIC) stimulated LH production to the same level as GnRH, and neither agent potentiated the effect of the releasing hormone. Cholera toxin and prostaglandin E1 (PGE1), both of which stimulated cAMP production in cultured pituicytes, did not raise LH levels as markedly as GnRH. These results demonstrate the independence of LH release from cAMP accumulation in cultured pituicytes, suggesting that cAMP is not required for stimulation of LH release from these cells and that GnRH acts on LH secretion by a different mechanism.  相似文献   

13.
In order to examine pituitary gonadotropin secretion and responsiveness to GnRH after photic-induced changes in reproductive condition, an in vitro pituitary perifusion system was established for male golden hamster tissue. Anterior pituitaries from adult males which had been maintained on 14 h light:10 h dark (long days) or 6 h light:18 h dark (short days) for 10 weeks were perifused using an Acusyst perifusion system. Perfusates from unstimulated tissue (basal secretion) and from tissue stimulated with hourly pulses of GnRH (25, 50, or 100 ng/ml) were assayed for LH and FSH by RIA. Tissue from short-day animals had lower basal LH secretion than tissue from long day animals, but there were no significant photoperiodic differences for GnRH-stimulated LH secretion. In contrast, there were no photoperiodic differences in basal FSH secretion, but tissue from short-day animals secreted more FSH than tissue from long-day animals when stimulated with GnRH. Bioactivity of a small number of perfusate samples was assessed using in vitro rat granulosa cell and mouse Leydig cell assays for FSH and LH, respectively, and did not show any photoperiodic differences in LH or FSH bioactivity for GnRH-stimulated tissue. These studies indicate that the pituitaries of gonadally regressed hamsters are capable in vitro of responding to GnRH with similar or greater levels of gonadotropin release compared to pituitaries from animals with functional gonads. Therefore, it appears that the lowered serum gonadotropin levels seen in vivo in gonadally regressed animals are not due to a reduction in intrinsic pituitary sensitivity to GnRH.  相似文献   

14.
To determine whether dihydrotestosterone (DHT) or estradiol (E2) exerts negative or positive feedback effects on rat pituitary gland, Testosterone (T) metabolite (T, DHT, 5 alpha-androstane-3 alpha, 17 beta-diol:3 alpha-diol or E2) was added to the cultured pituitary cells. Anterior pituitary glands were obtained from 6-week-old male rats. Pituitary cells were prepared by trypsin digestion and incubated with various concentrations of steroid hormones for 72 h to determine the effects of steroid hormones on basal secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) after 48 h preculture without steroids. Then 10 nM luteinizing hormone-releasing hormone (LH-RH) with appropriate concentrations of these steroid hormones was added to the pituitary cells in culture and incubated for another 6h to determine the effects of steroid hormones on LH-RH induced gonadotropin release. After the incubation, pituitary cells were lysed with 0.1% Triton X100 to measure the intracellular gonadotropin content. The concentration of LH and FSH was determined by radioimmunoassay. T, DHT and 3 alpha-diol stimulated basal FSH but not basal LH secretion, and inhibited both the release of FSH and LH from cultured pituitary cells during incubations with LH-RH in a dose-dependent fashion. Intracellular content of both FSH and LH were increased, and total FSH and not LH was also increased by the addition of DHT in a dose-dependent manner. E2 did not exert any of such effects on pituitary cells in culture. These studies suggest that 5 alpha-reduced metabolites but not aromatized metabolite of T play an important role on feedback regulation of gonadotropin secretion at pituitary level. DHT directly acts on pituitary gland not only to stimulate the production of FSH but also to suppress FSH and LH secretion induced by LH-RH.  相似文献   

15.
Neuropeptide Y (NPY) has recently been localized in the rat hypothalamus. We have evaluated the effects of NPY on hypothalamic and pituitary function by injecting NPY into the third ventricle in vivo and by examining its action on perifused pituitary cells in vitro. Injections of NPY into the third ventricle of conscious ovariectomized rats led to a dramatic and highly significant reduction in plasma luteinizing hormone (LH) relative to pretreatment levels in these animals or to those of controls injected with physiological saline. Significant inhibition was obtained with doses ranging from 0.02 to 5.0 micrograms (4.7-1175 pmol) of NPY. These inhibitory effects on LH release were dose dependent and lasted for at least 120 min after injection of 5.0 micrograms of NPY. Intraventricular injection of NPY also significantly decreased plasma growth hormone; however, the threshold dose was 2.0 micrograms (470 pmol), a dose 100-fold greater than the lowest dose that inhibited LH release. Plasma follicle-stimulating hormone was unaffected by injection of NPY. NPY (10(-6) and 10(-7) M) stimulated secretion of LH, growth hormone, and follicle-stimulating hormone from perifused anterior pituitary cells loaded in a Bio-Gel P-2 column. These results indicate that NPY acts on structures adjacent to the third ventricle to inhibit the secretion of LH and growth hormone but not follicle-stimulating hormone, whereas it can directly stimulate the secretion of all three hormones from the cells of the anterior pituitary in vitro. Since NPY has been found in the hypothalamus and median eminence, it is quite likely that it plays a physiologically significant role at both hypothalamic and pituitary sites: influencing secretion of pituitary hormones.  相似文献   

16.
L S Young  S I Naik  R N Clayton 《Endocrinology》1984,114(6):2114-2122
In this study the GnRH receptors (GnRH-R) in cultured rat pituitary cells were examined after treatment with GnRH and cyclic nucleotide derivatives. GnRH at doses of between 10(-11) and 10(-8) M caused GnRH-R increases, 10(-9) M resulting in a 50% stimulation of both GnRH-R and LH release. (Bu)2cAMP increased GnRH-R in a dose dependent manner, with a maximal 2-fold increase at 1 mM, with no effect on LH release in serum-containing medium. The time-course of both the GnRH and (Bu)2cAMP stimulation of GnRH-R was similar, with maximal levels being reached between 6-12 h. There was no difference in the GnRH receptor affinity subsequent to either GnRH or (Bu)2cAMP treatment. GnRH-R increases of 70% were observed when pituitary cells were treated with 1 mM cAMP and 8- bromocAMP , but n-butyric acid, adenosine, and cyclic guanosine monophosphate (all 1 mM) were not effective. Fifty eight millimolar KCl resulted in a 2-fold elevation of GnRH-R. Isobutylmethylxanthine (0.2 mM) did not affect basal receptor levels and slightly enhanced the GnRH-and potassium-stimulated increase of GnRH-R, whereas the increase caused by (Bu)2cAMP was completely prevented. Simultaneous treatment of cultured pituitary cells with either GnRH, KCl, or (Bu)2cAMP and cycloheximide completely prevented GnRH-R increases, while not affecting either basal or GnRH and KCl-stimulated LH secretion. None of the cyclic nucleotides stimulated LH release under the culture conditions employed to examine receptor regulation. However, when incubated in medium not containing serum, both (Bu)2cAMP and cyclic guanosine monophosphate stimulated significant LH release. When the pituitary cells were treated with GnRH in medium without serum, no increase in GnRH-R was measured, although LH release was unaffected. However, absence of serum in the medium did not affect either the K+ or (Bu)2cAMP stimulation of GnRH-R. The GnRH antagonist ( DpGlu1 , D-Phe2, D-Trp3,6) GnRH (1 microM) prevented both GnRH- and (Bu)2cAMP-induced increases in GnRH-R, although not that of 58 mM KCl. The antagonist also inhibited GnRH-stimulated LH secretion, although not that caused by KCl.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

17.
Gonadotropin-releasing hormone (GnRH) stimulated the formation of two major metabolites of the 5-lipoxygenase pathway, leukotriene (LT) B4 and LTC4, as well as luteinizing hormone (LH) release in primary cultures of rat anterior pituitary cells. Several lines of evidence suggested the presence of a GnRH-dependent pituitary endocrine system in which LTs act as second messengers for LH release: (i) GnRH-dependent LT formation was observed within 1 min and immediately preceded GnRH-induced LH release, whereas exogenous LTs stimulated LH release at low concentrations; (ii) the dose responses of GnRH-induced LT production and LH release were similar and both effects required the presence of extracellular Ca2+ ions; (iii) GnRH-induced LH release was blocked by up to 45% following the administration of several LT receptor antagonists; (iv) LTE4 action on LH secretion was entirely abolished by LT receptor antagonists; and (v) an activator of protein kinase C acted synergistically with LTE4 to induce LH release. The major source of LT formation in the pituitary cell cultures appeared to be the gonadotrophs, as shown by GnRH receptor desensitization experiments. The results demonstrate the presence of a GnRH-activatable 5-lipoxygenase pathway in anterior pituitary cells and provide strong support for the hypothesis that LTs play a role in LH release in the GnRH signaling pathway.  相似文献   

18.
The intrapituitary mechanisms underlying the inhibitory actions of hyperprolactinaemia on the reproductive axis remain unclear. Previous work on primary pituitary cultures revealed combined suppressive effects of prolactin (PRL) and dopamine on the gonadotrophin response to GnRH. However, whether these effects occur directly at the level of the gonadotroph and are accompanied by changes in gene expression is still unresolved. Here, alphaT(3)-1 and LbetaT2 cells were used to investigate the effects of PRL and dopamine on gonadotrophin synthesis and release in gonadotroph monocultures under basal and GnRH-stimulated conditions. PRL receptor and dopamine receptor mRNA expressions were first determined by RT-PCR in both cell lines. Then, PRL and the dopamine agonist bromocriptine (Br), alone or in combination, were shown to block the maximal alpha-subunit and LHbeta-subunit mRNA responses to a dose-range of GnRH. The LH secretory response was differentially affected by treatments. GnRH dose-dependently stimulated LH release, with a 4-5 fold increase at 10(-8) M GnRH. Unexpectedly, PRL or Br stimulated basal LH release, with PRL, but not Br, enhancing the LH secretory response to GnRH. This effect was, however, completely blocked by Br. These results reveal direct effects of PRL and dopamine at the level of the gonadotroph cell, and interactions between these two hormones in the regulation of gonadotrophin secretion. Moreover, uncoupling between LH synthesis and release in both the basal and the GnRH-stimulated responses to PRL and dopamine was clearly apparent.  相似文献   

19.
A variety of indirect data suggest that the luteinizing hormone (LH) lowering effects of ethanol (ETOH) are mediated at a hypothalamic level decreasing the synthesis and/or release of LH-releasing hormone (LHRH). Little direct data support this concept, however. The current study was, therefore, designed utilizing a perifusion system with frequent sampling for LHRH with and without ethanol added to determine if ethanol had a direct effect on basal or stimulated LHRH release. A variety of secretagogues, including dopamine, norepinephrine, naloxone, prostaglandin E2, and a high dose of potassium were utilized. Ethanol at a dose of 300 mg% did not alter either basal or secretagogue-stimulated LHRH release from the hypothalami of ethanol-naive male rats. Thus, ethanol did not appear to have a direct effect on LHRH in this system. Alterations in LHRH release by ethanol may occur at a suprahypothalamic level, involving neurotransmitter-LHRH interactions. Alternatively, the well-described lowering effect of ethanol on LH may be secondary to a direct pituitary locus of action, or involve a metabolic breakdown product of ethanol rather than ethanol itself.  相似文献   

20.
This study was designed to investigate the effects of penfluridol, a potent neuroleptic calmodulin inhibitor, on basal and secretagogue-stimulated secretion of thyroid-stimulating hormone (TSH), growth hormone (GH), and luteinizing hormone (LH). The drug had no effect on basal TSH or LH release, but decreased GH release in a dose-related manner. TSH, LH, and GH secretion stimulated by calcium ionophore A23187 or 50 mM K+ was decreased by penfluridol as was TSH and GH release stimulated by dibutyryl-cAMP (dbcAMP). Penfluridol reversibly abolished the stimulatory effect of thyrotropin-releasing hormone (TRH) on TSH release in perifused dispersed pituitary cells. The compound inhibited hormonal release without affecting hormonal synthesis and cellular morphology (trypan blue exclusion test). Penfluridol appears to inhibit hormonal secretion by interfering with the calcium-calmodulin system in the anterior pituitary; therefore calmodulin may be an important link in the stimulus-secretion coupling of adenohypophyseal hormones.  相似文献   

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