Fetal Leydig cell culture--an in vitro system for the study of trophic hormone and GnRH receptors and actions.
In fetal and neonatal rat Leydig cells cultured in the presence of LH, gonadotropin and GnRH receptors and acute testosterone responses to hCG, were maintained for up to 78 days. Addition of GnRH agonists markedly inhibited steroid production in LH-treated cultures, and abolished the acute testosterone response to hCG. GnRH receptors were not detectable in fetal testes but were present post-natally and increased markedly with age. In cultured fetal testis, GnRH receptors were detected on the third day, and were increased by exposure to GnRH agonists. In LH-treated cultures, GnRH sites were reduced by about 50% and did not increase during incubation with GnRH agonists. LH supported 17 alpha-hydroxylase/17-20 desmolase activities and pregnenolone formation were observed in short (1-4 days) and long-term cultures. Also, LH stimulation of 3 beta-hydroxysteroid dehydrogenase was observed by histochemical studies at 7 days of culture. GnRH agonists inhibited LH dependent steroid production in a dose-dependent fashion and abolished the acute testosterone response to human chorionic gonadotropin. The major component of the steroid inhibitory effect of GnRH agonist occurs beyond cAMP production. A distal lesion of the microsomal enzymes of the androgen pathway is largely responsible for the GnRH-induced decreases in LH-supported androgen production. The expression of functional GnRH receptors during culture and their suppression by LH suggest that pituitary gonadotropins exert a tonic inhibitory effect upon testicular GnRH receptors. The presence of functional GnRH receptors and inhibitory actions in cultured fetal and neonatal Leydig cells indicates that GnRH-related peptides can influence the actions of gonadotropins on the fetal Leydig cell population.
D019326:17-alpha-Hydroxyprogesterone; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006651:Histocytochemistry; D006908:Hydroxyprogesterones / Q000378:metabolism; D007700:Kinetics; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D011247:Pregnancy; D011284:Pregnenolone / Q000096:biosynthesis; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors
D006063:Chorionic Gonadotropin; D006908:Hydroxyprogesterones; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C010661:surfagon; D019326:17-alpha-Hydroxyprogesterone; D011284:Pregnenolone; D007986:Luteinizing Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase