Fauser B C, Hsueh A J
Department of Reproductive Medicine, School of Medicine, University of California, San Diego, La Jolla 92093.
Life Sci. 1988;43(17):1363-70. doi: 10.1016/0024-3205(88)90302-5.
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.
通过研究转化生长因子-β（TGF-β）对原代培养的新生大鼠睾丸细胞睾酮（T）生成的影响，探讨了TGF-β作为睾丸内调节因子的潜在作用。在无血清培养基中预孵育3天后，睾丸细胞再用激素处理3天。用人绒毛膜促性腺激素（hCG）（0.3 - 30 ng/ml）处理睾丸细胞，可引起T水平呈剂量依赖性增加，最大值比基线水平高出9倍以上。虽然单独的TGF-β不影响T水平，但当细胞与TGF-β共同处理时，观察到hCG刺激的T生成受到剂量依赖性抑制。最大抑制率大于85%，IC50值为5 ng/ml（2×10⁻¹⁰ M；n = 5次实验）。这种抑制作用在开始处理48小时后明显，并且在停止TGF-β处理细胞1天后可以逆转。TGF-β还降低了福斯高林和（Bu）₂cAMP诱导的T生成（降低超过85%），表明TGF-β可以抑制cAMP形成远端的类固醇生成。添加TGF-β可抑制hCG刺激的细胞将外源性添加的雄激素前体（孕酮（P）和17α-羟孕酮）转化为T。相反，在用TGF-β处理的培养物中内源性P的积累没有变化。由于在睾丸中发现了TGF-β样活性，观察到的TGF-β的抑制作用表明这种生长因子在睾丸内具有潜在的调节作用。
