Hepatic steroid hydroxylating enzymes are controlled by the sexually dimorphic pattern of growth hormone secretion in normal and dwarf rats

Abstract

In rats, the onset of the sexually dimorphic pattern of growth hormone (GH) secretion and increased hepatic GH-binding capacity at puberty are temporally correlated with the sex-dependent expression of some hepatic cytochrome P450 enzymes involved in steroid metabolism. There are indications that the expression of the GH receptor gene itself is dependent on the sexually differentiated pattern of GH secretion. However, the molecular mechanisms by which a given pattern of GH secretion turns on a specific set of genes in the hepatocyte are not yet understood. Studies of the cytochrome P450 2C gene subfamily in hypophysectomized rats and isolated hepatocytes suggest that one major mechanism of GH action in the liver occurs through modulation of gene transcriptional initiation. The occurrence, in dwarf rats and in rats treated neonatally with monosodium glutamate, of sex differences in GH secretion and liver steroid metabolism typical of normal rats, in spite of a 95% reduction in pituitary GH levels, is compatible with the notion that extremely low levels of circulating GH are sufficient to regulate the expression of liver steroid-metabolizing enzymes. This, together with the fact that single daily subcutaneous injections of GH are sufficient to masculinize the liver of a hypophysectomized rat, indicates that neither the amplitude nor the frequency of the GH pulse is recognized as male or female by the hepatocyte, but rather the complete and prolonged suppression (in males) or the persistence (in females) of circulating GH during the trough period after a GH surge.

Increased lactotrophs despite decreased somatotrophs in the dwarf (dw/dw) rat: a defect in the regulation of lactotroph/somatotroph cell fate?

“…These dw/dw rats secrete GH in the typical sexually dimorphic rodent pulsatile pattern, albeit with much lower peak amplitudes (Legraverend et al 1992), and respond acutely to GH secretagogues such as GH-releasing hormone (GHRH) or growth hormone releasing peptide-6 (GHRP-6) with a GH secretory response, reduced in proportion to their pituitary content , Carmignac & Robinson 1990). …”

Pituitary growth hormone network responses are sexually dimorphic and regulated by gonadal steroids in adulthood

“…sex hormones | body growth | calcium signaling | systems biology I n most species, males and females display a marked phenotypic divergence in body size, with increased growth rate and body mass being a predominantly masculine trait. Furthermore, in all species examined to date, the growth hormone (GH) axis demonstrates sex-specific differences in hormone contents, secretory outputs, and secretory patterns (1) and their effects on gene expression (2)(3)(4). The secretion of GH is controlled by hypothalamic GH-releasing hormone (GHRH) and somatostatin, and there is good evidence for sex-specific imprinting on hypothalamic hypophysiotropic neurons exerted by gonadal steroid exposure early in life (5), with ongoing effects during puberty (6).…”

Characterization of cDNAs encoding isoforms of hamster 3 beta-hydroxysteroid dehydrogenase/delta 5-->4 isomerase

“…The much greater expression of 3 -HSD in the male liver as opposed to the female liver would be consistent with this hypothesis. In itself this is not proof; the expression of many drug-metabolizing P450 s in the liver is sexually dimorphic (Legraverend et al 1992) and these enzymes do not appear to be involved in the metabolism of sex steroids. It has been established that 3 -reduction by the enzyme 3 -HSD is an important step in 5 -DHT metabolism (Toscano 1986).…”