Regulation of galanin gene expression in the rat anterior pituitary gland by the somatostatin analog SMS 201-995.
In addition to inducing pituitary tumors in rats, estrogen (E2) markedly increases galanin and PRL gene expression. We previously showed that galanin secretion from pituitary cells in vitro is inhibited by dopamine and somatostatin and stimulated by TRH. The objectives of these in vivo studies were to assess whether the long-acting somatostatin analog SMS 201-995 alters 1) immunoreactive galanin or PRL levels in the anterior pituitary, neurointermediate lobe, hypothalamus, or plasma, 2) pituitary galanin and PRL mRNA levels, and 3) the development of E2-induced pituitary tumors. Ovariectomized Fischer 344 rats were implanted with E2-filled or empty Silastic capsules and treated with or without SMS 201-995 (1.5 mg) via Alzet miniosmotic pumps. Two or 6 weeks later, immunoreactive galanin and PRL levels were determined by RIA. In ovariectomized rats, the somatostatin analog lowered the anterior pituitary content of galanin by 50%, but had no effect on PRL concentrations. E2 increased galanin and PRL levels in the anterior pituitary by 220- and 4-fold, respectively. Concomitant E2 and SMS 201-995 treatment further increased galanin and PRL in the anterior pituitary by 60-80%, but decreased plasma galanin and PRL levels. Likewise, the administration of SMS 201-995 for 2 and 6 weeks inhibited the E2-induced growth of the anterior pituitary. Galanin and PRL mRNA levels were quantified by solution hybridization. Galanin mRNA levels were reduced to undetectable levels in ovariectomized rats treated with SMS 201-995. Furthermore, a 10-fold increase in galanin mRNA levels seen in the presence of E2 was inhibited 80% by SMS 201-995. PRL mRNA levels in E2-treated rats were unchanged by SMS 201-995. We conclude that SMS 201-995 1) lowers plasma galanin and PRL levels in E2-treated rats, 2) elevates the anterior pituitary contents of galanin and PRL in E2-exposed rats, probably through decreased secretion of the hormones, and 3) reduces galanin mRNA levels in E2-treated and untreated ovariectomized rats. Overall, these results establish the differential regulation of galanin and PRL gene expression in vivo by SMS 201-995. Moreover, the data demonstrate that somatostatin receptor agonists may have therapeutic potential for some prolactinomas.
Hyde
J F
JF
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington 40536.
Howard
G
G
D000818:Animals; D004967:Estrogens / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D019004:Galanin; D005786:Gene Expression Regulation / Q000187:drug effects*; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D010052:Ovariectomy; D010455:Peptides / Q000032:analysis / Q000097:blood / Q000235:genetics*; D010903:Pituitary Gland, Anterior / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D011388:Prolactin / Q000032:analysis / Q000235:genetics / Q000502:physiology; D015175:Prolactinoma / Q000139:chemically induced / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D011916:Rats, Inbred F344
D004967:Estrogens; D010455:Peptides; D012333:RNA, Messenger; D019004:Galanin; D011388:Prolactin; D015282:Octreotide