Effect of transforming growth factor-beta on human chorionic gonadotropin induced testosterone production by cultured rat testicular cells.
The potential role of transforming growth factor-beta (TGF-beta) as an intragonadal regulator in the testis was investigated by studying the effect of TGF-beta on testosterone (T) production by neonatal rat testis cells in primary cultures. After 3 days of preincubation in serum-free medium, testis cells were treated with hormones for 3 additional days. Human chorionic gonadotropin (hCG) treatment (0.3-30 ng/ml) of testis cells elicited a dose-dependent increase of T levels with maximum values greater than 9-fold over baseline. Although TGF-beta alone did not affect T levels, a dose-dependent inhibition of hCG-stimulated T production was observed when cells were cotreated with TGF-beta. Maximal inhibition was greater than 85%, and the IC50 value was 5 ng/ml (2 x 10(-10) M; n = 5 experiments). This inhibitory effect was evident 48 h after the initiation of treatment and could be reversed 1 day after the cessation of TGF-beta exposure of cells. TGF-beta also reduced forskolin and (Bu)2cAMP-induced T production (greater than 85% decrease), indicating that TGF-beta can inhibit steroidogenesis distal to the formation of cAMP. The conversion of exogenously added androgen precursors (progesterone (P) and 17 alpha-hydroxyprogesterone) to T by hCG-stimulated cells was suppressed by the addition of TGF-beta. In contrast, endogenous P accumulation did not change in cultures treated with TGF-beta. Because TGF-beta-like activity has been found in the testis, the observed inhibitory effect of TGF-beta suggests a potential intratesticular regulatory role of this growth factor.
Fauser
B C
BC
Department of Reproductive Medicine, School of Medicine, University of California, San Diego, La Jolla 92093.
Hsueh
A J
AJ
D019326:17-alpha-Hydroxyprogesterone; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D006908:Hydroxyprogesterones / Q000378:metabolism; D008297:Male; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000166:cytology / Q000378:metabolism*; D013739:Testosterone / Q000096:biosynthesis*; D013997:Time Factors; D015291:Transforming Growth Factors / Q000502:physiology*
D006063:Chorionic Gonadotropin; D006908:Hydroxyprogesterones; D005576:Colforsin; D013739:Testosterone; D011374:Progesterone; D003994:Bucladesine; D019326:17-alpha-Hydroxyprogesterone; D015291:Transforming Growth Factors