GENE-EXPRESSION OF PROGESTERONE-RECEPTOR ISOFORMS IN THE RAT-BRAIN

Progesterone receptors (PRs) are known to exist in two forms: a larger molecular, form B, and a smaller one, form A. Rat PR cDNA corresponding to the region around the translation-initiation site (ATG(B)) of the putative PR form B mRNA was cloned, together with cloning of steroid-binding domain of the PR forms A and B. An imperfect ''estrogen responsive element,'' GGTCG*** TGACT, was located around ATG(B) of the rat PR cDNA. The distribution of PR mRNA-containing neurons was mapped in the female adult rat brain by and situ hybridization, which was largely in agreement with that of PR proteins. Differential intracerebral distribution of the mRNAs, measured by the quantitative RT-PCR Southern blotting assay, was found between the total(A + B) and form B mRNA levels, indicating possible distinct mechanisms responsible for regulation of the expression of the PR mRNAs. A region-specific and stage-related gene expression of the PR isoform system occurred in the developing rat brain: gene expression of form B seems predominantly to be ''turned on'' first around birth, followed by that of form A around Days 8-12. The postnatal developmental pattern of PR form B mRNA in the cerebral cortex resembled that of the PR proteins. Noninducibility of the cortical PR by estrogen might be ascribable to the predominance of form B mRNA, which was reported to have little or no estrogen inducibility. A missmatch existed between PR from A and its mRNA levels, suggesting some impairment of the synthesis of form A. Thyroid hormone may be a regulator of gene expression of the receptor in the developing cortex. (C) 1994 Academic Press, Inc.