Hypothalamo-pituitary regulation of cytochrome p-450_15β apoprotein levels in rat liver

The regulation of the sexually differentiated steroid sulfate 15β-hydroxylase, cytochrome P-450(15β) of female rat liver has been investigated. Specific antibodies raised to isozyme P-450(15β) were used with the Western blot technique to quantitate the specific levels of P-450(15β) 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(15β) is controlled by GH. Hypophysectomy of female animals resulted in a decrease of P-450(15β) 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(15β) level to that of the female. The same dose of human GH in hypophysectomized male or female animals raised the P-450(15β) 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(15β) levels, whereas infusion to rat GH caused a 4-fold increase. Thus, the regulation of P-450(15β) 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(15β) 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(15β) content, whereas neonatal castration led to a feminization of the P-450(15β) content in the adult male rat. Administration of estradiol valerate to male animals caused complete feminization of P-450(15β) levels, whereas administration of androgen to female animals caused a decrease to male levels. Before 21 days of age, the P-450(15β) level was slightly higher in male than in female rats. At 35 days, however, the P-450(15β) 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(15β) regulation. In conclusion, isozyme P-450(15β) 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.