• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Aug 1, 1991; 88(15): 6868–6872.
PMCID: PMC52190

Interpulse interval in circulating growth hormone patterns regulates sexually dimorphic expression of hepatic cytochrome P450.

Abstract

Plasma growth hormone (GH) profiles are sexually differentiated in many species and regulate the sex-dependence of peripubescent growth rates and liver function, including steroid hydroxylase cytochrome P450 expression, by mechanisms that are poorly understood. By use of an external pump to deliver to hypophysectomized rats pulses of rat GH of varying frequency and amplitude, a critical element for liver discrimination between male and female GH patterns was identified. Liver expression of the male-specific steroid 2 alpha (or 16 alpha)-hydroxylase P450, designated CYP2C11, was stimulated by GH at both physiological and nonphysiological pulse amplitudes, durations, and frequencies, provided that an interpulse interval of no detectable GH was maintained for at least 2.5 hr. This finding suggests that hepatocytes undergo an obligatory recovery period after stimulation by a GH pulse. This period may be required to reset a GH-activated intracellular signaling pathway or may relate to the short-term absence of GH receptors at the hepatocyte surface after a cycle of GH binding and receptor internalization. These requirements were distinguished from those necessary for the stimulation by GH of normal male growth rates in hypophysectomized rats, indicating that different GH responses and, perhaps, different GH-responsive tissues recognize distinct signaling elements in the sexually dimorphic patterns of circulating GH.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Tannenbaum GS, Martin JB. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology. 1976 Mar;98(3):562–570. [PubMed]
  • Johnson RJ. Diminution of pulsatile growth hormone secretion in the domestic fowl (Gallus domesticus): evidence of sexual dimorphism. J Endocrinol. 1988 Oct;119(1):101–109. [PubMed]
  • Asplin CM, Faria AC, Carlsen EC, Vaccaro VA, Barr RE, Iranmanesh A, Lee MM, Veldhuis JD, Evans WS. Alterations in the pulsatile mode of growth hormone release in men and women with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1989 Aug;69(2):239–245. [PubMed]
  • Winer LM, Shaw MA, Baumann G. Basal plasma growth hormone levels in man: new evidence for rhythmicity of growth hormone secretion. J Clin Endocrinol Metab. 1990 Jun;70(6):1678–1686. [PubMed]
  • Jansson JO, Edén S, Isaksson O. Sexual dimorphism in the control of growth hormone secretion. Endocr Rev. 1985 Spring;6(2):128–150. [PubMed]
  • Morgan ET, MacGeoch C, Gustafsson JA. Hormonal and developmental regulation of expression of the hepatic microsomal steroid 16 alpha-hydroxylase cytochrome P-450 apoprotein in the rat. J Biol Chem. 1985 Oct 5;260(22):11895–11898. [PubMed]
  • Kato R, Yamazoe Y, Shimada M, Murayama N, Kamataki T. Effect of growth hormone and ectopic transplantation of pituitary gland on sex-specific forms of cytochrome P-450 and testosterone and drug oxidations in rat liver. J Biochem. 1986 Oct;100(4):895–902. [PubMed]
  • Janeczko R, Waxman DJ, Le Blanc GA, Morville A, Adesnik M. Hormonal regulation of levels of the messenger RNA encoding hepatic P450 2c (IIC11), a constitutive male-specific form of cytochrome P450. Mol Endocrinol. 1990 Feb;4(2):295–303. [PubMed]
  • Waxman DJ, LeBlanc GA, Morrissey JJ, Staunton J, Lapenson DP. Adult male-specific and neonatally programmed rat hepatic P-450 forms RLM2 and 2a are not dependent on pulsatile plasma growth hormone for expression. J Biol Chem. 1988 Aug 15;263(23):11396–11406. [PubMed]
  • Norstedt G, Palmiter R. Secretory rhythm of growth hormone regulates sexual differentiation of mouse liver. Cell. 1984 Apr;36(4):805–812. [PubMed]
  • Noshiro M, Negishi M. Pretranslational regulation of sex-dependent testosterone hydroxylases by growth hormone in mouse liver. J Biol Chem. 1986 Dec 5;261(34):15923–15927. [PubMed]
  • MacLeod JN, Shapiro BH. Growth hormone regulation of hepatic drug-metabolizing enzymes in the mouse. Biochem Pharmacol. 1989 May 15;38(10):1673–1677. [PubMed]
  • Gustafsson JA, Mode A, Norstedt G, Skett P. Sex steroid induced changes in hepatic enzymes. Annu Rev Physiol. 1983;45:51–60. [PubMed]
  • Waxman DJ. Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression. Biochem Pharmacol. 1988 Jan 1;37(1):71–84. [PubMed]
  • Jansson JO, Frohman LA. Differential effects of neonatal and adult androgen exposure on the growth hormone secretory pattern in male rats. Endocrinology. 1987 Apr;120(4):1551–1557. [PubMed]
  • Pampori NA, Agrawal AK, Shapiro BH. Renaturalizing the sexually dimorphic profiles of circulating growth hormone in hypophysectomized rats. Acta Endocrinol (Copenh) 1991 Mar;124(3):283–289. [PubMed]
  • Shapiro BH, MacLeod JN, Pampori NA, Morrissey JJ, Lapenson DP, Waxman DJ. Signalling elements in the ultradian rhythm of circulating growth hormone regulating expression of sex-dependent forms of hepatic cytochrome P450. Endocrinology. 1989 Dec;125(6):2935–2944. [PubMed]
  • MacLeod JN, Shapiro BH. Repetitive blood sampling in unrestrained and unstressed mice using a chronic indwelling right atrial catheterization apparatus. Lab Anim Sci. 1988 Oct;38(5):603–608. [PubMed]
  • Waxman DJ, Ram PA, Notani G, LeBlanc GA, Alberta JA, Morrissey JJ, Sundseth SS. Pituitary regulation of the male-specific steroid 6 beta-hydroxylase P-450 2a (gene product IIIA2) in adult rat liver. Suppressive influence of growth hormone and thyroxine acting at a pretranslational leve;. Mol Endocrinol. 1990 Mar;4(3):447–454. [PubMed]
  • Waxman DJ. Rat hepatic P450IIA and P450IIC subfamily expression using catalytic, immunochemical, and molecular probes. Methods Enzymol. 1991;206:249–267. [PubMed]
  • Nebert DW, Nelson DR, Coon MJ, Estabrook RW, Feyereisen R, Fujii-Kuriyama Y, Gonzalez FJ, Guengerich FP, Gunsalus IC, Johnson EF, et al. The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol. 1991 Jan-Feb;10(1):1–14. [PubMed]
  • Mode A, Gustafsson JA, Jansson JO, Edén S, Isaksson O. Association between plasma level of growth hormone and sex differentiation of hepatic steroid metabolism in the rat. Endocrinology. 1982 Nov;111(5):1692–1697. [PubMed]
  • MacGeoch C, Morgan ET, Gustafsson JA. Hypothalamo-pituitary regulation of cytochrome P-450(15) beta apoprotein levels in rat liver. Endocrinology. 1985 Nov;117(5):2085–2092. [PubMed]
  • Waxman DJ, Morrissey JJ, LeBlanc GA. Female-predominant rat hepatic P-450 forms j (IIE1) and 3 (IIA1) are under hormonal regulatory controls distinct from those of the sex-specific P-450 forms. Endocrinology. 1989 Jun;124(6):2954–2966. [PubMed]
  • Ram PA, Waxman DJ. Hepatic P450 expression in hypothyroid rats: differential responsiveness of male-specific P450 forms 2a (IIIA2), 2c (IIC11), and RLM2 (IIA2) to thyroid hormone. Mol Endocrinol. 1991 Jan;5(1):13–20. [PubMed]
  • Ram PA, Waxman DJ. Pretranslational control by thyroid hormone of rat liver steroid 5 alpha-reductase and comparison to the thyroid dependence of two growth hormone-regulated CYP2C mRNAs. J Biol Chem. 1990 Nov 5;265(31):19223–19229. [PubMed]
  • Kato R. Sex-related differences in drug metabolism. Drug Metab Rev. 1974;3(1):1–32. [PubMed]
  • Goble FC. Sex as a factor in metabolism, toxicity, and efficacy of pharmacodynamic and chemotherapeutic agents. Adv Pharmacol Chemother. 1975;13:173–252. [PubMed]
  • Waxman DJ, Morrissey JJ, MacLeod JN, Shapiro BH. Depletion of serum growth hormone in adult female rats by neonatal monosodium glutamate treatment without loss of female-specific hepatic enzymes P450 2d (IIC12) and steroid 5 alpha-reductase. Endocrinology. 1990 Feb;126(2):712–720. [PubMed]
  • Leung DW, Spencer SA, Cachianes G, Hammonds RG, Collins C, Henzel WJ, Barnard R, Waters MJ, Wood WI. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature. 1987 Dec 10;330(6148):537–543. [PubMed]
  • Stred SE, Stubbart JR, Argetsinger LS, Shafer JA, Carter-Su C. Demonstration of growth hormone (GH) receptor-associated tyrosine kinase activity in multiple GH-responsive cell types. Endocrinology. 1990 Nov;127(5):2506–2516. [PubMed]
  • Rogers SA, Hammerman MR. Growth hormone activates phospholipase C in proximal tubular basolateral membranes from canine kidney. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6363–6366. [PMC free article] [PubMed]
  • Doglio A, Dani C, Grimaldi P, Ailhaud G. Growth hormone stimulates c-fos gene expression by means of protein kinase C without increasing inositol lipid turnover. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1148–1152. [PMC free article] [PubMed]
  • Bick T, Youdim MB, Hochberg Z. Adaptation of liver membrane somatogenic and lactogenic growth hormone (GH) binding to the spontaneous pulsation of GH secretion in the male rat. Endocrinology. 1989 Sep;125(3):1711–1717. [PubMed]
  • Bick T, Youdim MB, Hochberg Z. The dynamics of somatogenic and lactogenic growth hormone binding: internalization to Golgi fractions in the male rat. Endocrinology. 1989 Sep;125(3):1718–1722. [PubMed]
  • Roupas P, Herington AC. Cellular mechanisms in the processing of growth hormone and its receptor. Mol Cell Endocrinol. 1989 Jan;61(1):1–12. [PubMed]
  • Jansson JO, Albertsson-Wikland K, Edén S, Thorngren KG, Isaksson O. Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats. Acta Physiol Scand. 1982 Feb;114(2):261–265. [PubMed]
  • Charlton HM, Clark RG, Robinson IC, Goff AE, Cox BS, Bugnon C, Bloch BA. Growth hormone-deficient dwarfism in the rat: a new mutation. J Endocrinol. 1988 Oct;119(1):51–58. [PubMed]
  • Bullock P, Gemzik B, Johnson D, Thomas P, Parkinson A. Evidence from dwarf rats that growth hormone may not regulate the sexual differentiation of liver cytochrome P450 enzymes and steroid 5 alpha-reductase. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5227–5231. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...