| First Author | Jonak CR | Year | 2018 |
| Journal | Endocrinology | Volume | 159 |
| Issue | 3 | Pages | 1496-1510 |
| PubMed ID | 29409045 | Mgi Jnum | J:267477 |
| Mgi Id | MGI:6256709 | Doi | 10.1210/en.2017-00844 |
| Citation | Jonak CR, et al. (2018) GnRH Receptor Expression and Reproductive Function Depend on JUN in GnRH ReceptorExpressing Cells. Endocrinology 159(3):1496-1510 |
| abstractText | Gonadotropin-releasing hormone (GnRH) from the hypothalamus regulates synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gonadotropes. LH and FSH are heterodimers composed of a common alpha-subunit and unique beta-subunits, which provide biological specificity and are limiting components of mature hormone synthesis. Gonadotrope cells respond to GnRH via specific expression of the GnRH receptor (Gnrhr). GnRH induces the expression of gonadotropin genes and of the Gnrhr by activation of specific transcription factors. The JUN (c-Jun) transcription factor binds to AP-1 sites in the promoters of target genes and mediates induction of the FSHbeta gene and of the Gnrhr in gonadotrope-derived cell lines. To analyze the role of JUN in reproductive function in vivo, we generated a mouse model that lacks JUN specifically in GnRH receptorexpressing cells (conditional JUN knockout; JUN-cKO). JUN-cKO mice displayed profound reproductive anomalies such as reduced LH levels resulting in lower gonadal steroid levels, longer estrous cycles in females, and diminished sperm numbers in males. Unexpectedly, FSH levels were unchanged in these animals, whereas Gnrhr expression in the pituitary was reduced. Steroidogenic enzyme expression was reduced in the gonads of JUN-cKO mice, likely as a consequence of reduced LH levels. GnRH receptordriven Cre activity was detected in the hypothalamus but not in the GnRH neuron. Female, but not male, JUN-cKO mice exhibited reduced GnRH expression. Taken together, our results demonstrate that GnRH receptorexpression levels depend on JUN and are critical for reproductive function. |
