Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth
Malcolm J. Low, … , Yogesh C. Patel, Marcelo Rubinstein
Malcolm J. Low, … , Yogesh C. Patel, Marcelo Rubinstein
Published June 15, 2001
Citation Information: J Clin Invest. 2001;107(12):1571-1580. https://doi.org/10.1172/JCI11941.
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Article

Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

Abstract

Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth.

Authors

Malcolm J. Low, Veronica Otero-Corchon, Albert F. Parlow, Jose L. Ramirez, Ujendra Kumar, Yogesh C. Patel, Marcelo Rubinstein

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SST-deficient mice retain a normal sexual dimorphism in body size but ex...
SST-deficient mice retain a normal sexual dimorphism in body size but exhibit altered pituitary GH secretion. (a) Serial body weights of sibling Smst+/+ and Smst–/– mice (n = 16) generated from N5 B6 congenic Smst+/– parents demonstrate normal growth patterns. The small increase in weight of male Smst–/– mice after 18 weeks of age is due to increased white adipose tissue without organomegaly (n = 8) (data not shown). (b) Nose-to-anus body lengths of the mice in a at age 24 weeks are significantly different between sexes but not between genotypes. (c) Box plots of randomly obtained serum GH levels from N5 B6 congenic mice of each sex and genotype (n = 97–107) demonstrate significant differences among the median values of the four groups (P < 0.0001, Kruskal-Wallis test). Individual values in the upper and lower 10% of the population distributions are plotted as open circles. Data are expressed as nanograms per milliliter in terms of the mouse GH AFP10783B reference preparation. (d) Pituitary GH content at age 20 weeks (n = 4–7) of sibling Smst+/+ and Smst–/– mice generated from F2 hybrid Smst+/– parents is decreased by 50% in both sexes of Smst–/– mice. (e) Serum IGF-1 levels of the mice in d show no difference between genotypes when the data are collapsed across sex.