Growth hormone: a regulator of the sexually differentiated steroid metabolism in rat liver

Specific lesions in the periventricular area of the hypothalamus in male rats lead to a partial feminization of the liver steroid metabolism and a simultaneous reduction of the somatostatin level in the median eminence. Administration of an antiserum against somatostatin causes a similar degree of feminization of liver metabolism in male rats. Thus somatostatin could be the neuroendocrine regulator of the sexually differentiated metabolism of steroids in rat liver. A possible influence from the amygdaloid complex in regulating hepatic steroid metabolism is also indicated since large lesions in the amygdala cause a slight feminization of hepatic steroid metabolism in male rats. The female pattern of hepatic steroid metabolism is induced following frequent administration of hGH. The feminizing effect of hGH on hepatic steroid metabolism does not require the presence of gonads, adrenals, or thyroid. The somatogenic property of hGH seems to be responsible for the feminizing effect since purified rGH alone gives a complete feminization of hepatic steroid metabolism in hypophysectomized animals. rGH purified from male or female pituitary glands is equally efficient in feminizing hepatic steroid metabolism. Furthermore, male or female rGH have the same apparent molecular weight and isoelectric point. The mechanism whereby GH regulates hepatic steroid metabolism could be related to the sexually differentiated secretory profile of GH in the rat. A continuous presence of GH in the circulation seems to be a prerequisite for a female pattern of hepatic steroid metabolism. By analogy, it may be suggested that the high-peak, low-trough secretory pattern of GH characteristic of male rats causes a masculine type of liver steroid metabolism. Gonadal hormones affect both the secretory profile of GH and hepatic steroid metabolism. It is most probable that gonadal hormones affect liver steroid metabolism via modulations of the GH secretory profile. Possibly, estrogen exerts its effect directly on the pituitary by stimulating GH secretion. Androgen most probably has its primary site of action in the anterior hypothalamus or in extrahypothalamic areas. A plausible mechanism is that androgens stimulate the hypothalamic GH-inhibitory center. An overall view of the present hypothesis concerning hypothalamopituitary regulation of the sexually differentiated hepatic steroid metabolism in the rat is presented in Figure 2.