Hypothalamo-pituitary regulation of cytochrome p-45015β apoprotein levels in rat liver

Catriona Macgeoch, Edward T. Morgan, Jan-Ake Gustafsson

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2085-2092
Number of pages8
JournalEndocrinology
Volume117
Issue number5
DOIs
StatePublished - Jan 1 1985

ASJC Scopus subject areas

  • Endocrinology

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