Sex differences in PRA and PRB expression in the neonatal mouse brain.
Diana Lalitsasivimol1, Kalpana D Acharya2, Paige L Graney1
1Department of Psychology & Center for Neuroscience Research, University at Albany, Albany, New York, USA.
Journal of Neuroendocrinology
|January 7, 2026
Summary
Sex differences in brain progestin receptor (PR) expression emerge during development. Both PR isoforms, PRA and PRB, contribute to higher PR levels in male rodents, influencing sexually dimorphic behaviors.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- Significant sex differences exist in progestin receptor (PR) expression in the rodent medial preoptic nucleus (MPN) during development.
- Males exhibit high PR immunoreactivity (PR-ir) from embryonic day 19, while females show minimal PR until the second postnatal week.
- This developmental window suggests differential sensitivity to progestins between male and female MPN.
Purpose of the Study:
- To investigate the distinct roles of the two PR isoforms, PRA and PRB, in establishing sex differences in PR expression within the developing MPN.
- To compare PR-ir levels in neonatal male and female mice lacking either PRA (PRAKO) or PRB (PRBKO) with their wildtype (WT) counterparts.
- To examine PR isoform expression in other brain regions involved in reproductive neuroendocrine functions, such as the ventromedial nucleus of the hypothalamus (VMN) and arcuate nucleus (ARC).
Main Methods:
- Utilized knockout mouse models (PRAKO and PRBKO) to assess the contribution of each PR isoform.
- Quantified PR immunoreactivity (PR-ir) in the medial preoptic nucleus (MPN) of neonatal male and female knockout and wildtype mice.
- Analyzed PR isoform expression in the ventrolateral ventromedial nucleus of the hypothalamus (VMN) and arcuate nucleus (ARC).
Main Results:
- WT males consistently showed higher PR-ir in the MPN than WT females, confirming previous findings.
- Sex differences in MPN PR-ir were observed in both PRAKO and PRBKO mice, indicating contributions from both PRA and PRB isoforms to male PR expression.
- In the VMN and ARC, PRA was identified as the predominant isoform, with males expressing higher levels than females.
Conclusions:
- Both PRA and PRB isoforms play a role in the sex-specific expression of progestin receptors in the developing male MPN.
- Differential expression of PRA and PRB isoforms contributes to sex differences in PR levels within brain regions critical for sexually dimorphic behaviors and neuroendocrine functions.
