Inhibitory Control of the Pituitary LH Secretion by LH-RH in Male Rats

Sandow, J.; W, von Rechenberg; Kühl, Harald P.; Baumann, R; Krauss, Babett; Jerzabek, G.; Kille, S.

doi:10.1159/000179068

Cited by 19 publications

(5 citation statements)

References 25 publications

(29 reference statements)

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“…Organ accumulation of buserelin metabo¬ lites in liver and kidney is also not modified, but the increased uptake of 125I in the thyroid gland sug-gests enhanced degradation by non-pituitary tis¬ sues after long-term analogue treatment. It has recently been confirmed that in vivo the rat liver and kidney degrade buserelin within 60 min after injection to metabolites of greatly reduced biologi¬ cal activity (Sandow et al 1980). LH-release tested by a small constant dose of [125I]buserelin (similar to a diagnostic LRH test) is greatly reduced in group III after chronic buse¬ relin treatment.…”

Section: Discussionmentioning

confidence: 95%

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Hypothalamic-pituitary-testicular function in rats after supraphysiological doses of a highly active LRH analogue (buserelin)

Sandow¹,

Rechenberg²,

Jerzabek³

et al. 1980

Acta Endocrinologica

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Abstract. Male pre-pubertal rats (60 g) were treated with the LRH analogue, [D-Ser(But)6]LRH(1—9)-nonapeptide-ethylamide (buserelin, Hoe 766), during 4 weeks by daily sc injections of 5, 50 or 500 ng peptide (group I, II and III). At the end of treatment, hypothalamic LRH content and arylamidase activity (LRH degrading enzyme) were not changed. Pituitary arylamidase activity was reduced, but the pituitary LRH receptors (tested by analogue binding in vitro) were not diminished. Pituitary accumulation of [125I]buserelin 60 min after iv injection was not modified and organ distribution in liver and kidney was unchanged. Pituitary responsiveness to the analogue was reduced at the highest dose, but there was significant LH-release at all three dose levels. Testosterone production in vitro (stimulated by hCG) was unaltered in group I and dramatically reduced in group II and III. Testicular testosterone content and hCG binding by testes homogenates were dose-dependently reduced. Histology of the testes after 4 weeks treatment showed minimal impairment of spermatogenesis at the highest dose, whereas the epididymis was almost devoid of sperm. The results indicate, that low dose treatment with a highly active LRH analogue, buserelin, does not interfere with pituitary responsiveness (LRH receptors and LH-release) and testicular function (testosterone production, testosterone content, LH-receptor level). At higher doses, pituitary and testicular responsiveness are dose-dependently inhibited. At the pituitary level, LRH receptors were not reduced. The antifertility effect of supraphysiological doses at the testicular level is explained by an LH-dependent loss of LH-receptors.

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Section: Discussionmentioning

confidence: 95%

“…observation). The lack of concomitant FSH-suppression explains, why gona¬ dal involution induced by analogues is readily reversible (Sandow et al 1980).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic-pituitary-testicular function in rats after supraphysiological doses of a highly active LRH analogue (buserelin)

Sandow¹,

Rechenberg²,

Jerzabek³

et al. 1980

Acta Endocrinologica

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“…Conversely, when GnRH is administered continuously or chronically in large doses, LH responses to acute increments in GnRH are markedly reduced (116)(117)(118)(119)(120). Moreover, continuous infusion of GnRH into ovariectomized monkeys without endogenous GnRH secretion failed to reinstate gonadotropin secretion, whereas the same daily dose administered intermittently was rapidly effective in this regard (121).…”

Section: ) Receptor Regulation By Gnrh Agonists and Antagonistsmentioning

confidence: 99%

Gonadotropin-Releasing Hormone Receptors: Characterization, Physiological Regulation, and Relationship to Reproductive Function

1981

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“…The intermittent nature of the GnRH stimulus is essential for the maintenance ofLH secretion, and administration of GnRH by continuous infusion to experimental animals or humans results in desensitization of LH release (8)(9)(10). GnRH action on the gonadotroph is initiated by binding to specific membrane receptors (11), and calcium has been postulated as the second messenger involved in mediating LH release (12,13 Recently, cDNAs coding for LH a and /3 subunits were isolated (16,17), and we have used these cDNAs as hybridization probes to develop a sensitive assay for mRNAs using dot-blot hybridization of extracted cytoplasmic RNA from rat pituitaries.…”

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confidence: 99%

Gonadotropin-releasing hormone differentially regulates expression of the genes for luteinizing hormone alpha and beta subunits in male rats.

Papavasiliou¹,

Zmeili²,

Khoury³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

132

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Gonadotropin-releasing hormone (GnRH) and gonadal steroids regulate synthesis and release of luteinizing hormone (LH). GnRH is secreted intermittently by the hypothalamus, producing pulsatile LH release, and a pulsatile GnRH stimulus is required to maintain LH secretion. We report the regulatory effects of GnRH Recently, cDNAs coding for LH a and /3 subunits were isolated (16,17), and we have used these cDNAs as hybridization probes to develop a sensitive assay for mRNAs using dot-blot hybridization of extracted cytoplasmic RNA from rat pituitaries.We employed this mRNA quantitation assay to study the effects of GnRH pulse injections on expression of the genes for LH a and p subunits in gonadectomized male rats that were given testosterone implants. In this animal model endogenous GnRH secretion is markedly reduced, as judged by infrequent serum LH pulses (18). Thus assessment of the effects of exogenous GnRH pulse injections, given to mimic the intermittent physiologic stimulus, is not unduly complicated by endogenous GnRH secretion. In addition, experiments are performed in the presence of stable physiologic concentrations of testosterone, which avoids the potential effects of fluctuating serum testosterone levels in intact animals (19). This model has been previously used to study the effects of testosterone in regulating GfiRH receptor and gonadotropin responses to a pulsatile GnRH stimulus (19). In the present study we examined the effects of different doses of GnRH per pulse injection on GnRH membrane receptors and LH subunit gene expression to assess their role in the regulation of gonadotropin secretion. MATERIALS AND METHODSMale Sprague-Dawley rats (250-300 g) were castrated and implanted with two 20-mm Silastic implants containing testosterone, to produce a serum testosterone concentration of 2.3 ± 0.12 ng/ml (mean ± SEM). Beginning immediately after recovery from anesthesia, GnRH pulse (10-250 ng per pulse) or control saline injections were given every 30 min for 48 For mRNA quantification pituitaries were individually homogenized in 10 mM Tris/0.5% Nonidet P-40/1 mM EI)TA, pH 7.4, and the homogenate was centrifuged (13,000x g for 5 mmin). DNA was measured (20) in the nuclear pellet, and total RNA was extracted from the cytosol supernatant by using a phenol/chloroform/isoamyl alcohol mixture (100:100:1, Abbreviations: GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone. §To whom reprint requests should be addressed

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Inhibitory Control of the Pituitary LH Secretion by LH-RH in Male Rats

Cited by 19 publications

References 25 publications

Hypothalamic-pituitary-testicular function in rats after supraphysiological doses of a highly active LRH analogue (buserelin)

Hypothalamic-pituitary-testicular function in rats after supraphysiological doses of a highly active LRH analogue (buserelin)

Gonadotropin-Releasing Hormone Receptors: Characterization, Physiological Regulation, and Relationship to Reproductive Function

Gonadotropin-releasing hormone differentially regulates expression of the genes for luteinizing hormone alpha and beta subunits in male rats.

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