Cited by 163Growth Hormone and Insulin-like Growth FactorsHypothalamic control of reproductive hormonesPituitary Gland Disorders and Treatments

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

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Low, Malcolm J., Otero-Corchon, Veronica, Parlow, Albert F., Ramirez, Jose L., Kumar, Ujendra, Patel, Yogesh C., Rubinstein, Marcelo·2001·Journal of Clinical Investigation

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.

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Authors
Low, M. J., Otero-Corchon, V., Parlow, A. F., Ramirez, J. L., Kumar, U., Patel, Y. C., & Rubinstein, M.
Affiliations
  • Oregon Health & Science University (US)
  • University of California, Los Angeles (US)
  • Royal Victoria Hospital (CA)
  • Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
Corresponding author
Low, Malcolm J.
Venue
Journal of Clinical Investigation
Published
2001-06-15
Volume
107
Issue
12
Pages
1571-1580
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1981736657
Cited by
163
References
42
Citations by year
2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 9 · 2014: 9 · 2013: 8 · 2012: 2
FWCI
6.00
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Funders
  • Robert Wood Johnson Foundation
  • National Institutes of Health (5r01ns032160-06)
  • Canadian Institutes of Health Research
  • National Institute of Neurological Disorders and Stroke (NS32160)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
somatostatin, growth hormone secretion, sex differences, masculinization, hepatic gene expression, cytochrome P450, somatostatin receptors, hypothalamus, pituitary gland, physical growth, ultradian rhythms
MeSH terms
Animals, Body Weight, Female, Genotype, Hypothalamus, Liver, Male, Pituitary Gland, Recombination, Genetic, RNA, Messenger, Sex Characteristics, Somatostatin, Growth Hormone, Transcription, Genetic, Receptors, Somatostatin, Mice, Knockout, Mice

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