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

We previously showed that 17 beta-estradiol (E-2) induces the somatostatin (SRIF) responsiveness of the rat anterior pituitary, which leads to inhibition of PRL secretion through E-2-dependent SRIF receptors. To examine receptor subtypes regulated by E-2, 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 sst, and sst(2A) in ovariectomized rat pituitaries [sst(5)/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) = 1.4 x 10(-2), sst(2A)/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 sst(5) and sst(2A) in male rat pituitaries were higher than in females. chronic administration (4 weeks) of E-2 to the ovariectomized rats increased mRNA expression of sst(2A), sst(2B), sst(3), and sst(1) and drastically decreased expression of sst,; the transcripts of sst, isoforms constituted 87% of total SRIF receptor subtype mRNAs (sst(2A)/GAPDH = 1.2 x 10(-2)), whereas the sst(5) mRNA level was less than 1%. Receptor-binding studies revealed that in pituitaries from both ovariectomized rats and male rats, heterogeneous receptor types, probably sst(5) and sst(2), were expressed, whereas receptors from E-2-treated rat pituitaries mostly exhibited characteristics of the sst(2) subtype. The results demonstrated that sst(5) and sst(2A) were the major subtypes expressed in normal rat pituitaries with a sex-dependent difference and that whereas E-2 up-regulates the expression of sst(2) isoforms, it down-regulates the expression of sst(5), suggesting roles for these subtypes in the control of pituitary functions.