Differential regulation of FSH and inhibin gene expression and synthesis by testosterone in immature and mature male rats.
Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-D-pClPhe-D-pClPhe-D-Trp-Ser-Tyr-D-Arg-Leu-Arg-Pro-D-Ala-+ ++NH2CH3COOH (Ant; Organon 30276; 1.0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9.5 +/- 2.5 (S.E.M.) nmol/l to below the limit of detection (< 0.10 nmol/l; P < 0.01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-beta subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0.01). These levels were increased to 80-81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-beta subunit mRNA by 202% (P < 0.01). In intact immature rats Ant treatment decreased the level of pituitary FSH-beta subunit mRNA to 21% (P < 0.01), and a partial recovery (P < 0.01) to 42% of controls was observed with combined Ant+testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-beta subunit levels to 48% of controls (P < 0.01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common alpha or LH-beta subunits. In adult rats, the testicular inhibin alpha and beta A subunit mRNA levels were increased (P < 0.01) by Ant+testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant+testosterone treatment increased (P < 0.01) inhibin beta A subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level fo peripheral inhibin immunoreactivity from 8.3 +/- 2.0 U/ml to 2.1 +/- 0.4 U/ml (P < 0.01) and testosterone reversed it to 5.8 +/- 0.6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Physiology, University of Turku, Finland.
A
A
Perheentupa
M
M
Bergendahl
F H
FH
de Jong
I
I
Huhtaniemi
D000818:Animals; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D037201:Follicle Stimulating Hormone, beta Subunit; D005786:Gene Expression Regulation / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007265:Inhibins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009919:Orchiectomy; D010902:Pituitary Gland / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000502:physiology; D013268:Stimulation, Chemical; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D037201:Follicle Stimulating Hormone, beta Subunit; D012333:RNA, Messenger; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007265:Inhibins; C042691:LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone