Evidence That Gonadotropin-Releasing Hormone Stimulates Gene Expression and Levels of Active Nitric Oxide Synthase Type I in Pituitary Gonadotrophs, a Process Altered by Desensitization and, Indirectly, by Gonadal Steroids*
| Autor: | Yannick Lerrant, Raymond Counis, Claude Bouchaud, Ghislaine Garrel, Solange Magre, Annette Bérault, Céline Siriostis |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Agonist endocrine system Pituitary gland medicine.medical_specialty medicine.drug_class Blotting Western Gene Expression Gonadotropin-releasing hormone Gonadotropic cell Gonadotropin-releasing hormone antagonist Gonadotropin-Releasing Hormone Endocrinology Pituitary Gland Anterior Internal medicine medicine Animals Testosterone RNA Messenger Rats Wistar Triptorelin Pamoate Estradiol Histocytochemistry Chemistry NADPH Dehydrogenase Drug Tolerance Triptorelin Rats Isoenzymes Kinetics medicine.anatomical_structure Hypothalamus Nitric Oxide Synthase Gonadotropin Orchiectomy hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Endocrinology. 139:2163-2170 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | To determine the site and mechanism of action of gonadal steroids on pituitary nitric oxide synthase type I (NOS I), present in both gonadotrophs and folliculo-stellate cells, the effects of castration and steroids were examined in male rats, in the presence of a GnRH antagonist (Antarelix). Western analysis showed a rapid and substantial increase with time, after orchidectomy, of NOS I protein, the concentration doubling in 24 h and reaching a maximal 4- to 5-fold increase after 3-7 days, followed by a progressive decline after 2 weeks. Testosterone or estradiol replacement, or administration of GnRH antagonist, totally abolished the effects of castration, demonstrating a mediation of the steroid effects via GnRH. In noncastrated rats, steroids and the GnRH antagonist also caused a reduction in the levels of NOS I (by 50-60%), consistent with inhibition of endogenous GnRH stimulation. In marked contrast, administration of a potent GnRH agonist (Triptorelin) to intact rats increased the levels of NOS I. A time-course study with a long-lasting formulation showed that rise in NOS I developed rapidly after a lag of approximately 5 h, with a 2-fold increase detectable after 8 h and a maximal 4.5-fold after 48 h. The level declined afterwards in a manner consistent with homologous desensitization that may occur in the continuous presence of GnRH; however, the profile was different and delayed compared with those of gonadotropin release. As observed for NOS I protein, NOS I messenger RNA concentration was increased by castration or GnRH agonist and reduced by steroids or GnRH antagonist. Taken together, these data demonstrate that steroids indirectly regulate NOS I messenger RNA and protein levels, through the hypothalamic modulation of GnRH, which represents the primary regulator of NOS I. No effect of steroids on NOS I was seen in the posterior lobe. NADPH-diaphorase histochemistry coupled to immuno-identification of the cells revealed that the treatments affecting the concentration of NOS I concomitantly altered the activity but exclusively in gonadotrophs and not in folliculo-stellate cells (which do not respond to GnRH), reinforcing the idea that GnRH played a major regulatory role. Expression in gonadotrophs of a GnRH-dependent NOS I and the ensuing production of nitric oxide represents a potentially novel signaling pathway for the neuropeptide in the anterior pituitary, consistent with the previously reported GnRH-induced cGMP production, the role of which remains to be evaluated. |
| Databáze: | OpenAIRE |
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