Chronic treatment with estrogen up-regulates expression of sst2 messenger ribonucleic acid (mRNA) but down-regulates expression of sst5 mRNA in rat pituitaries.

Abstract

We previously showed that 17beta-estradiol (E2) induces the somatostatin (SRIF) responsiveness of the rat anterior pituitary, which leads to inhibition of PRL secretion through E2-dependent SRIF receptors. To examine receptor subtypes regulated by E2, we determined the messenger ribonucleic acid (mRNA) levels of all subtypes using a semiquantitative RT-PCR and characterized pituitary membrane receptors using subtype-preferential SRIF analogs. Most of the SRIF receptor subtype mRNAs were sst5 and sst2A in ovariectomized rat pituitaries [sst5/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) = 1.4 x 10(-2), sst2A/GAPDH = 0.4 x 10(-2)]. The expression pattern of the subtypes in ovariectomized rat pituitaries was similar to that of normal male and female rat pituitaries, although the mRNA levels of sst5 and sst2A in male rat pituitaries were higher than in females. Chronic administration (4 weeks) of E2 to the ovariectomized rats increased mRNA expression of sst2A, sst2B, sst3, and sst1 and drastically decreased expression of sst5; the transcripts of sst2 isoforms constituted 87% of total SRIF receptor subtype mRNAs (sst2A/GAPDH = 1.2 x 10(-2)), whereas the sst5 mRNA level was less than 1%. Receptor-binding studies revealed that in pituitaries from both ovariectomized rats and male rats, heterogeneous receptor types, probably sst5 and sst2, were expressed, whereas receptors from E2-treated rat pituitaries mostly exhibited characteristics of the sst2 subtype. The results demonstrated that sst5 and sst2A were the major subtypes expressed in normal rat pituitaries with a sex-dependent difference and that whereas E2 up-regulates the expression of sst2 isoforms, it down-regulates the expression of sst5, suggesting roles for these subtypes in the control of pituitary functions.