Androgen and progestogen production by prepubertal rat interstitial cells: study of the effects of LHRH and its analogues and their interactions with LH.
The effects of luteinizing hormone-releasing hormone (LHRH) and an agonistic analogue (LHRHa) have been examined in freshly isolated prepubertal rat interstitial cells and in cells precultured for 6 days in the presence or absence of luteinizing hormone (LH). C19-steroid output (testosterone and androstenedione), C21-steroid output (mainly progesterone and 20 alpha-hydroxypregn-4-en-3-one) and cyclic AMP secretion were used as parameters of interstitial cell activity. A potent 5 alpha-reductase inhibitor was added to the incubation media to simplify the pattern of steroid secretion. It could be demonstrated that LHRHa uniformly stimulates C21-steroid production whereas C19-steroid output is increased only in freshly isolated cells and in cells precultured with LH. At suboptimal concentrations of LH, LHRH and its agonist again uniformly potentiate C21-precursor production whereas LH-induced androgen production is slightly inhibited in freshly isolated cells, strongly inhibited in cells precultured in the absence of LH and markedly enhanced in cells precultured in the presence of LH. The concentrations (ED50 values) of the oligopeptides required to elicit these synergistic or antagonistic effects with LH are lower than those required for their direct effects. An antagonistic LHRH analogue blocks all the stimulatory and inhibitory activities of LHRHa. None of these activities is accompanied by noticeable changes in cyclic AMP secretion. Evidence is presented that LHRH and its agonistic analogue have a stimulatory effect early in the steroidogenic pathway and an inhibitory effect at the level of the conversion of C21-precursors into androgens. Our data suggest that the existing level of 17 alpha-hydroxylase and/or 17,20-desmolase activity is the major factor that determines the ultimate effect of LHRHa on androgen secretion.
D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D011372:Progestins / Q000096:biosynthesis*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation
D000728:Androgens; D011372:Progestins; D007987:Gonadotropin-Releasing Hormone; C010661:surfagon; C034511:LHRH, pGlu(1)-Phe(2)-Trp(3,6)-; D007986:Luteinizing Hormone; D011761:Pyrrolidonecarboxylic Acid