Colony-stimulating factor 1 regulation of neuroendocrine pathways that control gonadal function in mice.
Colony stimulating factor 1 (CSF-1) is the primary regulator of cells of the mononuclear phagocytic lineage. Consequently mice lacking CSF-1 (Csf1(op)/Csf1(op)) have depleted populations of macrophages in many tissues. In addition, both sexes have reduced fertility with females having extended estrus cycles and poor ovulation rates, whereas males have low circulating LH and T. In this study, we show that puberty was significantly delayed in Csf1(op)/Csf1(op) females compared with control littermates. Restoration of circulating CSF-1 over the first 2 wk of life accelerated puberty, and this treatment until puberty completely corrected the extended estrous cycles. In a standard LH surge induction protocol, Csf1(op)/Csf1(op) females showed diminutive negative and no positive feedback response to E2. These data, together with that from male Csf1(op)/Csf1(op) mice that showed normal release of LH with a GnRH agonist, indicate that the hypothalamus is the site of the primary defect causing fertility problems in CSF-1-deficient mice. In the hypothalamus, microglia are the only CSF-1 receptor-bearing cells, and the recruitment of a full complement these cells is slightly delayed in Csf1(op)/Csf1(op) mice. These data suggest a role for CSF-1 and its target cells, microglia, in establishing the feedback sensitivity to circulating steroid hormones in the hypothalamus of mice.
Cohen
Paula E
PE
Center for the Study of Reproductive Biology and Women's Health, Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Zhu
Liyin
L
Nishimura
Kayoko
K
Pollard
Jeffrey W
JW
D000818:Animals; D030762:Estrous Cycle / Q000502:physiology; D005246:Feedback / Q000502:physiology; D005260:Female; D006066:Gonads / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000097:blood; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009490:Neurosecretory Systems / Q000502:physiology*; D010022:Osteopetrosis / Q000235:genetics; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D012741:Sexual Maturation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013256:Steroids / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000502:physiology
D013256:Steroids; D016173:Macrophage Colony-Stimulating Factor; D007986:Luteinizing Hormone