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Publication : Lack of AR in LepRb Cells Disrupts Ambulatory Activity and Neuroendocrine Axes in a Sex-Specific Manner in Mice.

First Author  Cara AL Year  2020
Journal  Endocrinology Volume  161
Issue  8 PubMed ID  32609838
Mgi Jnum  J:294177 Mgi Id  MGI:6452177
Doi  10.1210/endocr/bqaa110 Citation  Cara AL, et al. (2020) Lack of AR in LepRb Cells Disrupts Ambulatory Activity and Neuroendocrine Axes in a Sex-Specific Manner in Mice. Endocrinology 161(8)
abstractText  Disorders of androgen imbalance, such as hyperandrogenism in females or hypoandrogenism in males, increase risk of visceral adiposity, type 2 diabetes, and infertility. Androgens act upon androgen receptors (AR) which are expressed in many tissues. In the brain, AR are abundant in hypothalamic nuclei involved in regulation of reproduction and energy homeostasis, yet the role of androgens acting via AR in specific neuronal populations has not been fully elucidated. Leptin receptor (LepRb)-expressing neurons coexpress AR predominantly in hypothalamic arcuate and ventral premammillary nuclei (ARH and PMv, respectively), with low colocalization in other LepRb neuronal populations, and very low colocalization in the pituitary gland and gonads. Deletion of AR from LepRb-expressing cells (LepRbDeltaAR) has no effect on body weight, energy expenditure, and glucose homeostasis in male and female mice. However, LepRbDeltaAR female mice show increased body length later in life, whereas male LepRbDeltaAR mice show an increase in spontaneous ambulatory activity. LepRbDeltaAR mice display typical pubertal timing, estrous cycles, and fertility, but increased testosterone levels in males. Removal of sex steroid negative feedback action induced an exaggerated rise in luteinizing hormone in LepRbDeltaAR males and follicle-stimulating hormone in LepRbDeltaAR females. Our findings show that AR can directly affect a subset of ARH and PMv neurons in a sex-specific manner and demonstrate specific androgenic actions in the neuroendocrine hypothalamus.
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