Hypothalamo-pituitary regulation of cytochrome P-450(15) beta apoprotein levels in rat liver.

The regulation of the sexually differentiated steroid sulfate 15 beta-hydroxylase, cytochrome P-450(15) beta of female rat liver has been investigated. Specific antibodies raised to isozyme P-450(15) beta were used with the Western blot technique to quantitate the specific levels of P-450(15) beta in liver microsomes. The method demonstrated that the levels of the protein are about 16-fold higher in female than in male microsomes and also showed that the specific microsomal content of P-450(15) beta is controlled by GH. Hypophysectomy of female animals resulted in a decrease of P-450(15) beta to male levels. Continuous infusion of human GH, mimicking the female pattern of GH secretion in intact male animals, caused an elevation of the P-450(15) beta level to that of the female. The same dose of human GH in hypophysectomized male or female animals raised the P-450(15) beta level 8-fold or 50% of that seen in normal females. Infusion of ovine PRL to intact male rats had no effect on P-450(15) beta levels, whereas infusion of rat GH caused a 4-fold increase. Thus, the regulation of P-450(15) beta by GH is mainly associated with the somatogenic properties of the hormone. Furthermore, sc injection of rat GH every 12 h, mimicking the male pattern of GH secretion, had no effect on P-450(15) beta levels, demonstrating the importance of the GH secretory pattern in regulation of the specific protein levels. Postpubertal castration of male animals did not influence the microsomal P-450(15) beta content, whereas neonatal castration led to a feminization of the P-450(15) beta content in the adult male rat. Administration of estradiol valerate to male animals caused complete feminization of P-450(15) beta levels, whereas administration of androgen to female animals caused a decrease to male levels. Before 21 days of age, the P-450(15) beta level was slightly higher in male than in female rats. At 35 days, however, the P-450(15) beta level in female rats had increased almost 100-fold, whereas the levels in males increased only slightly. These changes are concomitant with the development of the sexual differentiation of the GH secretory pattern, supporting the role of GH in P-450(15) beta regulation. In conclusion, isozyme P-450(15) beta is a GH-regulated enzyme specific for female rats. The low level of the protein in males is probably explained by neonatal androgenic programming of the GH secretory pattern.