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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adults male rats were implanted subcutaneously for 1, 2 or 4 days with Alzet osmotic minipumps, infusing synthetic gonadotropin-releasing hormone (GnRH) at a rate of 0.1 microgram/h. Plasma LH increased significantly, reaching a maximum after 2 days treatment. Plasma and testicular testosterone levels increased to a maximum in 1 day, and decreased gradually thereafter, reaching the control level by day 4. Testicular specific [125I]hCG binding decreased gradually during the treatment, being 57% of the controls by day 4. It is concluded that changes of physiologic magnitude in circulatory LH are able to induce a significant loss of testicular LH/hCG binding capacity. Furthermore, after a short stimulatory phase there is a lack of response in testicular steroidogenesis to the elevated LH levels.
Mol Cell Endocrinol
PMID:Rat testis LH/hCG recptors and testosterone production after treatment with GnRH. 21 64

Inhibition of plasma prolactin levels by 2-bromo-alpha-ergocryptine (CB-154) caused a 60% decrease and potentiated the inhibitory effects of [D-Ala6,des-Gly-NH2(10)]LHRH ethylamide on testicular LH receptor levels. Animals treated with the LHRH agonist showed reduced plasma and testicular testosterone levels and elevated progesterone concentration. This progesterone rise was further increased in animals having high circulating prolactin levels but was prevented by CB-154. These data demonstrate that: (1) treatment with the LHRH agonist induces a blockage in the steroidogenic pathway at a step between progesterone and testosterone and (2) prolactin levels to an apparent accentuation of this blockage reflected by higher progesterone levels.
Mol Cell Endocrinol 1979 Jan
PMID:Down-regulation of testicular androgen biosynthesis and LH receptor levels by an LHRH agonist: role of prolactin. 22 Dec 86

Castration of male rats decreased cAMP levels, and increased cGMP levels and gonadotropin release from anterior pituitaries incubated in vitro. Testosterone (T) replacement via silastic tubes filled with the steroid increased cAMP and decreased cGMP levels and gonadotropin release. Incubation of hemipituitaries from intact males with luteinizing hormone releasing hormone (LHRH, 5 nM for 2 h) resulted in increased cAMP and cGMP accumulation and gonadotropin release. Castration abolished LHRH-induced cAMP accumulation, but increased the effect of LHRH on cGMP accumulation and gonadotropin release. Testosterone replacement restored cAMP stimulation by LHRH but decreased LHRH-induced elevation of cGMP levels and gonadotropin release. These data illustrate parallel increases by castration of LHRH-induced cGMP accumulation and of gonadotropin release. Furthermore, these two parameters are influenced in the opposite direction by replacement therapy. These results support the concept of a role for cGMP in LHRH action as well as providing evidence of a link between the feedback action of T and cGMP in the pituitary gland.
Mol Cell Endocrinol 1979 Jun
PMID:Differential effects of castration and testosterone replacement on basal and LHRH-stimulated cAMP and cGMP accumulation and on gonadotropin release from the pituitary of the male rat. 22 2

The in vitro response of pituitaries isolated from both normal and 18-21 day post-castration male and female intact rats to incremental doses of synthetic gonadotropin-releasing hormone (LH-RH) has been investigated. Intact male pituitaries released luteinizing hormone (LH) maximally at the smallest dose of LH-RH (0.1 ng/ml) whereas intact female pituitaries released LH in a dose-response fashion. FSH release from intact male pituitaries was considerably greater than that from intact female pituitaries. As with LH, intact male pituitaries appeared maximally stimulated at 0.1 ng/ml of LH-RH. Intact female pituitaries did not release FSH until a 10 ng/ml dose of LH-RH was used. Male and female castrate pituitaries were more susceptible to LH-RH-induced LH and FSH release than were their intact counterparts, although this was more pronounced with regard to LH release. In addition castrate male pituitaries were more sensitive to lower doses of LH-RH than were castrate female pituitaries, this being most pronounced regarding LH release. Castrate female pituitaries released less FSH at the 100 ng/ml dose than at the 10 ng/ml dose, possibly indicating inhibition at these higher doses. In addition, pituitary extraction and serum from normal and castrate male and female rats were examined for LH and FSH content. LH content of castrated rat pituitaries of both sexes was considerably greater than that of their intact counterparts, as expected. However, castrate male pituitaries contained significantly less FSH than intact male pituitaries, whereas the opposite was true for the female groups. Serum LH and FSH levels were increased in the castrate groups with no difference between sexes. Serum from intact males contained considerably more FSH than did the serum from intact females.
Mol Cell Endocrinol 1975 Jul
PMID:In vitro pituitary responsiveness to gonadotropin-releasing hormone (LH-RH) in intact and castrated male and female rats. 109 78

Acute (0.5-4 h) treatment of estradiol (E)-primed female rat pituitary cells with progesterone (P) augments gonadotropin-releasing hormone (GnRH)-induced LH release, whereas chronic (48 h) P-treatment reduces pituitary responsiveness to the hypothalamic decapeptide. Dispersed E-primed (48 h, 1 nM) rat pituitary cells were cultured for 4 or 48 h in the presence of 100 nM P to assess the effects of the progestagen on GnRH receptors and on gonadotrope responsiveness to the decapeptide. P-treatment (4 h) significantly augmented GnRH-receptor concentrations (4.44 +/- 0.6 fmol/10(6) cells) as compared to cells treated only with E (2.6 +/- 0.5 fmol/10(6) cells). Parallel significant changes in GnRH-induced LH secretion were observed. The acute increase in GnRH-receptor number was nearly maximal (180% of receptor number in cells treated with E alone) within 30 min of P addition. Chronic P-treatment (48 h) significantly reduced pituitary responsiveness to GnRH as compared to E-treatment. The GnRH-receptor concentrations (3.9 +/- 0.6 fmol/10(6) cells), however, remained elevated above those in E-primed cells. GnRH-receptor affinity was not influenced by any of the different treatments. These results indicate that the acute facilitatory P-effect on GnRH-induced LH release is at least chronologically closely related to an increase in GnRH-receptor concentration. The chronic negative P-effect on pituitary responsiveness to GnRH, however, shows no relation to changes in available GnRH receptors.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Effects of progesterone on gonadotropin-releasing hormone receptor concentration in cultured estrogen-primed female rat pituitary cells. 132 17

Gonadal steroids act at the pituitary to regulate gonadotropin-releasing hormone (GnRH) receptor number and the responsiveness of gonadotropes to GnRH and can act at post-receptor sites to modulate Ca(2+)-mediated and protein kinase C-mediated signal-transducing pathways. However, such effects have been seen in the mixed cell population of primary cell cultures and may involve indirect effects on cells other than gonadotropes. Here, steroid effects on a recently described gonadotrope-derived cell line (alpha T3-1 cells) have been assessed. In these cells estradiol, progesterone, testosterone and corticosterone all exerted trophic effects. Estradiol increased [3H]thymidine incorporation with an EC50 of 10(-12) to 10(-11) M and this effect was blocked by keoxifene, an estrogen receptor antagonist. Estradiol also reduced binding of [125I]buserelin (EC50 approximately 10(-11) M), an effect which appears to reflect a reduction in GnRH receptor number rather than a change in Kd. Estradiol also shifted the dose-response curve for GnRH-stimulated inositol phosphate (IP) accumulation rightward, increasing the EC50 for this GnRH effect by approximately 20-fold. Accordingly estradiol acts directly upon alpha T3-1 cells not only to reduce GnRH receptor number, but also to reduce the efficiency of coupling of residual GnRH receptors to second messenger generation.
Mol Cell Endocrinol 1992 Sep
PMID:Estradiol regulates gonadotropin-releasing hormone receptor number, growth and inositol phosphate production in alpha T3-1 cells. 133 8

Endothelins (ET-1, ET-2, ET-3 and vasoactive intestinal contractor, VIC) and sarafotoxins (SRTX-b and SRTX-c) appear to bind with high affinity to a homogeneous class of binding sites in cultured rat pituitary cells. All of these ligands seem to interact with the same receptor (ETA-R), except for SRTX-c which apparently binds to a separate receptor. Binding was followed by phosphodiesteric cleavage of phosphoinositides, resulting in the formation of inositol phosphates. No consistent effect on basal or gonadotropin-releasing hormone (GnRH)-induced release of luteinizing hormone (LH) was exerted by ET or SRTX during 2 h of static incubation. On the other hand, both groups of vasoactive peptides inhibited basal and thyrotropin-releasing hormone (TRH)-induced prolactin secretion. Surprisingly, activation of phosphoinositide turnover by TRH in pituitary mammotrophs led to stimulation of prolactin secretion, whereas activation of the same pathway by ET or SRTX resulted in inhibition of prolactin secretion. ET and SRTX stimulated inositol phosphate formation in GH3 cell line and in the gonadotroph-like cell line alpha T-3 (which is capable of producing the alpha subunit of the gonadotrophins), indicating that the peptides interact with both pituitary mammotrophs and gonadotrophs. The very low concentrations (nM range) needed to stimulate phosphoinositide turnover and to inhibit prolactin secretion, as well as the recent finding that ETs are present in the hypothalamo-pituitary axis suggest that ET might participate in the neuroendocrine modulation of pituitary functions. One such possibility is that ETs might be members of the prolactin inhibiting factors (PIFs) family.
Mol Cell Endocrinol 1992 Nov
PMID:Paradoxical signal transduction mechanism of endothelins and sarafotoxins in cultured pituitary cells: stimulation of phosphoinositide turnover and inhibition of prolactin release. 133 19

A series of novel gonadotropin releasing hormone (GnRH) and Somatostatin analogs have been developed in our laboratory and were screened for antiproliferative and signal transduction inhibitory effect. Our GnRH analog Folligen, had significant antitumor activity on DMBA induced mammary carcinomas in rats without blocking ovarian functions. The direct effect of Folligen and Buserelin has been compared on the human breast cancer cell line MDA-MB-231. Folligen was found to be more effective in inhibiting cell proliferation and significant differences were found in the signal transduction pathways activated by these analogs. Our novel Somatostatin analogs were screened for tyrosine kinase inhibition and for antiproliferative effect on human colon tumor cells and for growth hormone (GH) release inhibition in vitro and in vivo. The analog TT-2-50 was significantly more active inhibiting GH release in superfused rat pituitary cells and in vivo than native Somatostatin and it strongly inhibited tyrosine kinase and proliferation while it stimulated protein kinase C activity.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Novel antitumor peptide hormones and their effect on signal transduction. 135 11

The release of gonadotropin-releasing hormone (GnRH) from the median eminence (ME) in cyclic rats was stimulated to a significant extent by the selective muscarinic antagonists 11[(2)(diethylamino)methyl][-1-piperidinyl]-acetyl-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX-116) and methoctramine, and to a lesser extent also by other ligands selectively antagonistic to m1 and m3 receptors. Such stimulation was estrous-cycle-dependent and was not achieved by muscarinic agonists. We suggest that the effect is induced via the m4 receptor subtype. Attempts to block the muscarinic-antagonist-induced stimulation of GnRH release with a variety of drugs were successful only in the presence of prazosin, an antagonist to alpha 1-adrenergic receptors. One possible explanation for this muscarinically mediated stimulation of GnRH release is that it results from cross-talk between the muscarinic and the alpha 1-adrenergic receptors, i.e., muscarinic agonists might inhibit the release induced by alpha 1-agonists, and muscarinic antagonists, by cancelling this inhibitory effect, might thus allow the endogenous alpha 1-agent, norepinephrine, to induce the release of GnRH.
Mol Cell Endocrinol 1992 Dec
PMID:Muscarinic involvement in the regulation of gonadotropin-releasing hormone in the cyclic rat. 136 91

In cultured pituitary gonadotrophs, gonadotropin-releasing hormone (GnRH) caused dose-dependent and biphasic increases in cytoplasmic calcium concentration ([Ca2+]i) and LH release. Both extra- and intracellular calcium pools participate in GnRH-induced elevation of [Ca2+]i and LH secretion. The spike phase of the [Ca2+]i response represents the primary signal derived predominantly from the rapid mobilization of intracellular Ca2+. In contrast, the prolonged phase of the Ca2+ signal depends exclusively on Ca2+ entry from the extracellular pool. The influx of Ca2+ occurs partially through dihydropyridine-sensitive calcium channels. Both [Ca2+]i and LH responses to increasing concentrations of GnRH occur over very similar time scales, suggesting that increasing degrees of receptor occupancy are transduced into amplitude-modulated Ca2+ responses, which in turn activate exocytosis in a linear manner. However, several lines of evidence indicated the complexity over the relationship between Ca2+ signaling and LH exocytosis. In contrast to [Ca2+]i measurements in cell suspension, single cell Ca2+ measurements revealed the existence of a more complicated pattern of Ca2+ response to GnRH, with a biphasic response to high agonist doses and prominent oscillatory responses to lower GnRH concentrations, with a log-linear correlation between GnRH dose and the frequency of Ca2+ spiking. In addition, analysis of the magnitudes of the [Ca2+]i and LH responses of gonadotrophs to a wide range of GnRH concentrations in the presence and absence of extracellular Ca2+, and to K+ and phorbol ester stimulation, showed non-linearity between these parameters with amplification of [Ca2+]i-mediated exocytosis. Studies on cell depleted of protein kinase C under conditions that did not change the LH pool suggested the participation of protein kinase C in this amplification, especially during the plateau phase of the secretory response to GnRH.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Calcium signaling and secretory responses in agonist-stimulated pituitary gonadotrophs. 137 99


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