Singh H, Thomas P
University of Texas, Austin Marine Science Institute, Port Aransas 78373.
Gen Comp Endocrinol. 1993 Mar;89(3):341-53. doi: 10.1006/gcen.1993.1042.
The mechanism of growth hormone's (bovine growth hormone, bGH) stimulatory action on steroidogenesis was examined using ovarian tissue of spotted seatrout (Cynoscion nebulosus) in an in vitro incubation system and compared to that of a gonadotropin (human chorionic gonadotropin, hCG). Testosterone and estradiol production by seatrout ovaries in vitro were stimulated even with low concentrations of bGH (50 ng/ml), and increasing concentrations demonstrated a concentration-dependent relationship similar to that observed with hCG. The steroidogenic responses to combined treatments with bGH and hCG approximately equaled the sum of the stimulatory effects of the two hormones, possibly indicating that bGH does not potentiate the action of gonadotropin. Cyanoketone treatment of vitellogenic follicles inhibited bGH-induced estradiol production, but the stimulatory effect of bGH on the conversion of exogenous testosterone to estradiol was not altered by cyanoketone, which suggests that GH stimulates aromatase activity in addition to an earlier step in the biosynthetic pathway for estradiol production. The stimulatory effects of bGH and hCG on aromatase activity were mimicked by forskolin and dibutyryl cAMP, both of which are known to raise the intracellular level of cAMP. These results suggest that bGH- as well as hCG-induced increases in aromatase activity are mediated through adenylate cyclase-cAMP-dependent mechanism(s). The cAMP content of ovarian follicles was markedly increased within 15 min of bGH stimulation and was maximal at 1 hr, whereas steroid production did not increase significantly until 30 min and was maximal after 3 to 9 hr of incubation. The cAMP response to bGH, like that of steroid production, was concentration-dependent. The time-course and concentration-response effects of bGH on cAMP accumulation and steroid production were similar to those of hCG and forskolin, although the magnitude of the responses was less. The addition of cycloheximide or actinomycin D to the media did not affect the basal production of estradiol but completely blocked the bGH and hCG stimulation of the aromatization of exogenous testosterone to estradiol. These results suggest that the stimulatory effects of bGH and hCG on aromatase activity depend upon the synthesis of new RNA and regulatory protein(s).
利用斑点海鲈(犬牙石首鱼)的卵巢组织,在体外孵育系统中研究了生长激素(牛生长激素,bGH)对类固醇生成的刺激作用机制,并与促性腺激素(人绒毛膜促性腺激素,hCG)的作用机制进行了比较。即使使用低浓度的bGH(50 ng/ml),也能刺激海鲈卵巢体外产生睾酮和雌二醇,并且浓度增加呈现出与hCG相似的浓度依赖性关系。bGH和hCG联合处理的类固醇生成反应大致等于两种激素刺激作用之和,这可能表明bGH不会增强促性腺激素的作用。用氰酮处理卵黄生成卵泡可抑制bGH诱导的雌二醇产生,但氰酮并未改变bGH对外源睾酮转化为雌二醇的刺激作用,这表明GH除了在雌二醇生物合成途径的早期步骤起作用外,还能刺激芳香化酶活性。 Forskolin和二丁酰cAMP模拟了bGH和hCG对芳香化酶活性的刺激作用,已知这两种物质均可提高细胞内cAMP水平。这些结果表明,bGH以及hCG诱导的芳香化酶活性增加是通过腺苷酸环化酶 - cAMP依赖性机制介导的。bGH刺激后15分钟内,卵巢卵泡的cAMP含量显著增加,1小时时达到最大值,而类固醇生成直到30分钟才显著增加,孵育3至9小时后达到最大值。bGH对cAMP的反应与类固醇生成一样,呈浓度依赖性。bGH对cAMP积累和类固醇生成的时间进程和浓度反应效应与hCG和Forskolin相似,尽管反应幅度较小。向培养基中添加环己酰亚胺或放线菌素D不影响雌二醇的基础产生,但完全阻断了bGH和hCG对外源睾酮芳香化为雌二醇的刺激作用。这些结果表明,bGH和hCG对芳香化酶活性的刺激作用取决于新RNA和调节蛋白的合成。