Developmental androgen excess disrupts reproduction and energy homeostasis in adult male mice.

Abstract

Polycystic ovary syndrome is a common endocrine disorder in females of reproductive age and is believed to have a developmental origin in which gestational androgenization programs reproductive and metabolic abnormalities in offspring. During gestation, both male and female fetuses are exposed to potential androgen excess. In this study, we determined the consequences of developmental androgenization in male mice exposed to neonatal testosterone (NTM). Adult NTM displayed hypogonadotropic hypogonadism with decreased serum testosterone and gonadotropin concentrations. Hypothalamic KiSS1 neurons are believed to be critical to the onset of puberty and are the target of leptin. Adult NTM exhibited lower hypothalamic Kiss1 expression and a failure of leptin to upregulate Kiss1 expression. NTM displayed an early reduction in lean mass, decreased locomotor activity, and decreased energy expenditure. They displayed a delayed increase in subcutaneous white adipose tissue amounts. Thus, excessive neonatal androgenization disrupts reproduction and energy homeostasis and predisposes to hypogonadism and obesity in adult male mice.

• Authors: Kazunari Nohara, Suhuan Liu, Matthew S Meyers, Aurélie Waget, Mathieu Ferron, Gérard Karsenty, Rémy Burcelin, Franck Mauvais-Jarvis
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 219 Issue 3 Pg. 259-68 (Dec 2013) ISSN: 1479-6805 [Electronic] England
• PMID: 24084835 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Environmental Pollutants
• Gonadotropins
• Kiss1 protein, mouse
• Kisspeptins
• Nerve Tissue Proteins
• Testosterone
• testosterone enanthate

Topics

• Adiposity (drug effects)
• Androgens (toxicity)
• Animals
• Animals, Newborn
• Behavior, Animal (drug effects)
• Energy Metabolism (drug effects)
• Environmental Pollutants (toxicity)
• Gonadotropins (blood)
• Hypogonadism (chemically induced, metabolism, pathology, physiopathology)
• Hypothalamus (drug effects, metabolism, pathology)
• Infertility, Male (etiology)
• Kisspeptins (metabolism)
• Male
• Mice
• Motor Activity (drug effects)
• Nerve Tissue Proteins (metabolism)
• Neurons (drug effects, metabolism, pathology)
• Obesity (chemically induced, metabolism, pathology)
• Subcutaneous Fat, Abdominal (drug effects, metabolism, pathology)
• Testosterone (analogs & derivatives, blood, toxicity)