Progesterone and its ring A reduced metabolites regulate female sexual behavior through the direct or indirect activation of
progesterone receptor (PR) which has two
isoforms with different function and regulation: PR-A and PR-B. The contribution of each PR
isoform to the regulation of
lordosis in rats is unknown. We explored the role of PR
isoforms in
lordosis display induced by
progesterone and two of its ring A reduced metabolites: 5alpha-pregnan-3,20-dione (5alpha-DHP), and 5beta,3beta-pregnan-20-one (5beta,3beta-Pgl) in adult ovariectomized rats. Two weeks after
ovariectomy, the animals were injected subcutaneously with 5 microg of
estradiol benzoate (EB), and 40 h later,
progestins were injected intracerebroventricularly. PR-B and total PR (PR-A + PR-B) sense or
antisense oligonucleotides were administered intracerebroventricularly immediately before EB injection and 24 h later.
Lordosis was evaluated 30, 120 and 240 min after
progestin administration. Western blot analysis of both PR
isoforms was performed in the hypothalamus and preoptic area 24 h after
lordosis tests. All
progestins induced maximal
lordosis 120 min after administration, and
antisense oligonucleotides against both PR
isoforms inhibited
lordosis in all animals. PR-B
antisense oligonucleotides also inhibited
lordosis induced by
progesterone and
5alpha-DHP although with less efficacy than total PR
antisense oligonucleotides, but the former inhibited
lordosis induced by 5beta,3beta-Pgl in a similar manner as total PR
antisense oligonucleotides. In the hypothalamus and preoptic area, the content of both PR
isoforms or PR-B alone was diminished by the administration of total or PR-B
antisense oligonucleotides, respectively. These results suggest that the PR-B
isoform is essential for the display of the
lordosis behavior in rats.