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The Relationship between Steroidogenic Factor 1 and DAX-1 Expression and in Vitro Gonadotropin Secretion in Human Pituitary Adenomas¹

Departments of Endocrinology (S.J.B.A., D.F.W., G.M.B., A.B.G., J.P.M.), Clinical Biochemistry (J.P.W., C.L.D., J.M.B.), and Morbid Anatomy (J.F.G.), St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London EC1A 7BE, United Kingdom

Address all correspondence and requests for reprints to: Dr. S. J. B. Aylwin, Department of Clinical Biochemistry, Molecular Endocrinology, Lab 1.4, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, London EC1A 7BE, United Kingdom. E-mail: saylwin{at}mds.qmw.ac.uk

Abstract

The orphan nuclear receptors, steroidogenic factor 1 (SF-1) and DAX-1, are involved in gonadotroph differentiation, and SF-1 has been shown to activate the LH-ß and glycoprotein hormone -subunit (GSU) gene promoters. Pituitary adenomas from 34 patients [13 somatotroph tumors, 4 prolactinomas, and 17 clinically nonfunctioning pituitary adenomas (NFPAs)] were enzymatically dispersed and cultured in vitro for 48 h. Tissue culture medium was collected and assayed for LH, FSH, and GSU; messenger RNA was extracted from adherent cells, and expression of SF-1 and DAX-1 messenger RNA was determined by RT-PCR and verified by direct DNA sequencing. The presence of DAX-1 protein in tumor tissue was confirmed by immunocytochemistry.

DAX-1 was demonstrated in all NFPAs, 7 of 13 somatotroph tumors and 0 of 4 prolactinomas. SF-1 expression occurred in 8 of 16 NFPAs, 4 of 12 somatotroph tumors, and 1 of 4 prolactinomas. LH secretion in vitro was greater in NFPAs that were SF-1 positive (P < 0.05). Neither FSH secretion nor GSU secretion in vitro were significantly related to the expression of SF-1 or DAX-1. SF-1-positive somatotroph tumors immunostained positively for LH-ß and/or FSH-ß and secreted gonadotropins in vitro.

SF-1 expression is associated with the in vitro secretion of LH by NFPAs. A proportion of somatotroph tumors also express SF-1 and DAX-1 and secrete gonadotropin hormones in vitro.

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