THE ONTOGENY OF GENE-EXPRESSION OF PROGESTIN RECEPTORS IN THE FEMALE RAT-BRAIN

The postnatal development of the progestin receptor (PR) system in the rat brain is a region-specific and stage-related process. In an attempt to analyze the molecular mechanism by which the dramatic change of gene expression of the PR occurs we have examined the level of PR mRNAs in the hypothalamus-preoptic area (HPOA) and cerebral cortex in development from fetal to postnatal stages of female rats. We used polymerase chain reaction to clone, from uterine cDNA, the cDNA corresponding to the steroid-binding domain of the PR forms 'A' and 'B' mRNA as well as the region around the translation-initiation site (ATG1) of the putative PR form 'B' mRNA. A quantitative reverse transcription-polymerase chain reaction assay was used to measure the level of mRNAs for PR forms 'A' and 'B' (total PR mRNAs) and PR form 'B'. There was a regional difference in the intracerebral distribution between the total and form 'B' mRNAs, indicating possible distinct mechanisms responsible for regulating the expression of the PR mRNAs. The PR mRNAs in the brain, already detectable 2 days before birth, increased at early neonatal stages. The total PR mRNAs in the cortex developed in a manner essentially similar to the PR protein at the early stages, but, surprisingly, unlike the receptor, the messages remained high at the later stages from day 18 to 8 weeks of life. On the other hand, the ontogeny of the cortical mRNA for form 'B', which predominantly existed in the region, resembled that of the cortical PR protein. In the HPOA the postnatal development of the form 'B' mRNAs was also roughly similar to the PR. These results suggest region-specific and stage-related gene expression of the PR isoform system in the developing brain: gene expression of form 'B' seems to be predominantly, first, ''turned on'' around birth, followed by form 'A' mRNA expression around days 8-12. Moreover, lowered levels of the cortical PR mRNAs in the propylthiouracil-induced hypothyroid rat, together with suppressed PR level, indicate a possible regulatory role of thyroid hormone on gene expression of the cortical receptor.