Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice

Xiaolin Chen, Lili Huang, Hwee Y. Tan, Hongzhuo Li, Ying Wan, Michael Cowley, Johannes D Veldhuis, Chen Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Deletion of the melanocortin-4-receptor (Mc4r) gene in mice causes hyperphagia, followed by hyperinsulinemia, obesity and progressive infertility. Evidence shows that the number of developed corpora lutea is reduced in obese MC4R-knockout (MC4R KO) female mice, but the mechanism is unclear. The effect of hyperphagia and obesity by MC4R KO on pulsatile luteinizing hormone (LH) secretion and ovulation remains unknown. In MC4R KO mice and wild-type littermates (WT LM) during the diestrus period throughout different ages, we examined and monitored their metabolic status, pulsatile LH profiles, follicular morphology and the number of corpora lutea. MC4R KO mice were hyperphagic, obese, hyperglycemic, hyperinsulinemic and demonstrated insulin resistance and hepatic steatosis. Irregular estrous cycles and significant changes in the LH secretion profiles were observed in sexually matured 16- to 28-week MC4R KO mice, without any difference in testosterone levels. In addition, MC4R KO mice at 16 weeks of age had significantly fewer corpora lutea than same age WT LM mice. The ovary examinations of MC4R KO mice at 28 weeks of age showed predominantly antral and preovulatory follicles with no corpora lutea. These findings were consistent with the decrease in total, pulsatile, mass and basal LH releases in MC4R KO mice. The characteristics of hormone profiles in obese MC4R KO mice indicate that MC4R plays an important role in regulating LH release, ovulation and reproductive ability probably via hyperphagia-induced obesity. Further study of correlation between metabolic and reproductive regulatory hormones is warranted to dissect the pathological mechanism underlying obesity-induced infertility.

Original languageEnglish (US)
Pages (from-to)267-276
Number of pages10
JournalReproduction
Volume153
Issue number3
DOIs
StatePublished - 2017

Fingerprint

Receptor, Melanocortin, Type 4
Knockout Mice
Luteinizing Hormone
Corpus Luteum
Hyperphagia
Obesity
Ovulation
Infertility
Hormones
Diestrus
Estrous Cycle
Hyperinsulinism
Insulin Resistance
Testosterone
Ovary

ASJC Scopus subject areas

  • Embryology
  • Reproductive Medicine
  • Endocrinology
  • Obstetrics and Gynecology
  • Cell Biology

Cite this

Chen, X., Huang, L., Tan, H. Y., Li, H., Wan, Y., Cowley, M., ... Chen, C. (2017). Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice. Reproduction, 153(3), 267-276. https://doi.org/10.1530/REP-16-0341

Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice. / Chen, Xiaolin; Huang, Lili; Tan, Hwee Y.; Li, Hongzhuo; Wan, Ying; Cowley, Michael; Veldhuis, Johannes D; Chen, Chen.

In: Reproduction, Vol. 153, No. 3, 2017, p. 267-276.

Research output: Contribution to journalArticle

Chen, X, Huang, L, Tan, HY, Li, H, Wan, Y, Cowley, M, Veldhuis, JD & Chen, C 2017, 'Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice', Reproduction, vol. 153, no. 3, pp. 267-276. https://doi.org/10.1530/REP-16-0341
Chen, Xiaolin ; Huang, Lili ; Tan, Hwee Y. ; Li, Hongzhuo ; Wan, Ying ; Cowley, Michael ; Veldhuis, Johannes D ; Chen, Chen. / Deficient melanocortin-4 receptor causes abnormal reproductive neuroendocrine profile in female mice. In: Reproduction. 2017 ; Vol. 153, No. 3. pp. 267-276.
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