EFFECT OF 17-BETA-ESTRADIOL ON SOMATOSTATIN RECEPTOR EXPRESSION AND INHIBITORY EFFECTS ON GROWTH-HORMONE AND PROLACTIN-RELEASE IN RAT PITUITARY CELL-CULTURES

In the present study, we tested whether 17 beta-estradiol (E-2)-induce d PRL sensitivity to somatostatin-14 (SRIF) involves selective upregul ation of discrete somatostatin receptor subtypes (ssts) in primary cul tures of female rat pituitary cells. The efficacy of the endogenous pe ptide SRIF to inhibit GH and PRL secretion and cAMP accumulation was c ompared with those of octreotide (OCT), BIM-23052, BIM-23056, and BIM- 23268, which have been reported to be relatively selective for rat sst 2, sst3, and sst5. Experiments were performed in steroid-depleted medi a supplemented or not with 1 nM E-2 for 96 h. SRIF, OCT, and BIM-23052 inhibited cAMP accumulation and GH release independently of E-2. In c ontrast, all three agonists affected PRL release in E-2-treated cultur es only. Inhibition of cAMP accumulation by SRIF, OCT, and BIM-23052 w as enhanced by exposure of cells to E-2. The rank of potency of the ag onists, OCT = SRIF > BIM-23052, was similar for GH and PRL inhibition, BIM-23268 was a weak agonist on GH, but not on PRL, secretion. BIM-23 056 had no effect on the release of either hormone, but slightly inhib ited cAMP formation in E-2-treated cells. To verify whether SRIF recep tor gene expression correlated with these observations, messenger RNA (mRNA) transcripts corresponding to the five ssts were measured by qua ntitative RT-PCR in the presence or absence of E-2. Control cells expr essed predominantly sst2 and ssts transcripts; sst1 mRNA was present i n moderate amounts, whereas sst4 and sst5 were only weakly expressed. E-2 had a differential effect on distinct ssts; it increased mRNA conc entrations corresponding to sst2 and sst3, and decreased that of sst1. These results indicate that sst2 and ssts receptors are the major som atostatin receptors expressed in the female rat pituitary, and that bo th of them are positively regulated by estradiol. However, the capacit y of lactotropes to respond to SRIF after exposure to E-2 seems to dep end more upon E-2-induced upregulation of the sst2 than of the sst3 re ceptor subtype.