Progesterone receptor A and B messenger ribonucleic acid levels in the anterior pituitary of rats are regulated by estrogen

In target tissues of most mammalian and avian species, progesterone recepto rs (PR) are expressed as structurally related, but functionally distinct, i soforms A and B, and they are regulated by estrogen (E) as well as by their cognate ligand, progesterone (P-4). The objectives of the present work wer e to identify mRNA expression for the A and B isoforms of PR in the anterio r pituitary of the rat, to examine its regulation by gonadal steroids, and to compare this regulation with that in the primary target organ, the uteru s. Messenger RNAs for the PR isoforms, determined by two separate reverse t ranscription-polymerase chain reaction protocols, one that detects PR A and PR B equally and the other specific for PR B, were identified in anterior pituitary of female and male rats. In anterior pituitary of cycling female rats, steady-state mRNA levels for both PR A+B and PR B were highest at 090 0 h on proestrus, declined rapidly to nadir values at 0900 h on metestrus ( PR A+B) or 0900 h on estrus (PR B), and remained below proestrous values th rough 2100 h on diestrus. Administration of E to intact proestrous female r ats caused significant increases in mRNA for both PR A+B and PR B on estrus and metestrus. Blockade of P-4 action by administration of the antiprogest ins RU-486 and ZK-98299 on proestrus had no effect on PR mRNA levels on the morning of estrus. Ovariectomy two and ten days after surgery markedly red uced mRNA levels for both PR A+B and PR B. Whereas treatment of 10-day-ovar iectomized rats with E led to marked induction of mRNA for PR A+B and PR B two days later, treatment with P-4 one day after treatment had no effect on basal or E-stimulated PR mRNA. Regulation of PR mRNA expression in the pit uitary differed from that in the uterus, in which P-4 treatment of ovariect omized rats antagonized the E-induced rise in mRNA for PR B, and antiproges tins increased mRNA for both isoforms. In addition to induction of PR mRNA in the pituitary of female rats by E in vivo, we also demonstrated inductio n by E in primary culture of anterior pituitary cells in vitro. We conclude that in the anterior pituitary of female rats, both the A and B isoforms o f PR are expressed and regulated by E.