Abstract
The possible signaling role of prokineticin 2 (PK2) and its receptor, prokineticin receptor 2 (PKR2), on female reproduction was investigated. First, the expression of PKR2 and its co-localization with estrogen receptor (ERα) in the hypothalamus was examined. Sexually dimorphic expression of PKR2 in the preoptic area of the hypothalamus was observed. Compared to the male mice, there was more widespread PKR2 expression in the preoptic area of the hypothalamus in the female mice. The likely co-expression of PKR2 and ERα in the preoptic area of the hypothalamus was observed. The estrous cycles in female PK2-null, and PKR2-null heterozygous mice, as well as in PK2-null and PKR2-null compound heterozygous mice were examined. Loss of one copy of PK2 or PKR2 gene caused elongated and irregular estrous cycle in the female mice. The alterations in the estrous cycle were more pronounced in PK2-null and PKR2-null compound heterozygous mice. Consistent with these observations, administration of a small molecule PK2 receptor antagonist led to temporary blocking of estrous cycle at the proestrous phase in female mice. The administration of PKR2 antagonist was found to blunt the circulating LH levels. Taken together, these studies indicate PK2 signaling is required for the maintenance of normal female estrous cycles.
Highlights
The estrous cycle is an important characteristic of the mammalian female reproductive system
We have previously shown that prokineticin receptor 2 (PKR2) is expressed in the preoptic area [24]
To further demonstrate prokineticin 2 (PK2) signaling may regulate female reproduction, we carried out the detailed analysis of PKR2 expression in the preoptic area in both males and females
Summary
The estrous cycle is an important characteristic of the mammalian female reproductive system. The expression of PKR2 in the preoptic area of the hypothalamus of adult mice suggests that PK2 signaling may have a direct signaling role in the control of the reproductive axis [10], in addition to its indirect developmental effect. This notion was supported by the observations that human subjects with heterozygous mutations in PK2 or PKR2 presented with complete isolated GnRH deficiency[17]. We took advantage of a newly developed small molecule PKR2 antagonist to explore the PK2 signaling roles in the reproductive axis of female mice
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.