Original Articles: Hormones and Reproductive Health
The Relationship between Steroidogenic Factor 1 and DAX-1 Expression and in Vitro Gonadotropin Secretion in Human Pituitary Adenomas1
S. J. B. Aylwin,
J. P. Welch,
C. L. Davey,
J. F. Geddes,
D. F. Wood,
G. M. Besser,
A. B. Grossman,
J. P. Monson and
J. M. Burrin
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, andSF-1 has been shown to
activate the LH-ß and glycoproteinhormone -subunit (GSU) gene
promoters. Pituitary adenomas from34 patients [13 somatotroph tumors,
4 prolactinomas, and 17clinically nonfunctioning pituitary adenomas
(NFPAs)] were enzymaticallydispersed and cultured in
vitro for 48 h. Tissue culture mediumwas collected and
assayed for LH, FSH, and GSU; messenger RNAwas extracted from
adherent cells, and expression of SF-1 andDAX-1 messenger RNA was
determined by RT-PCR and verified bydirect DNA sequencing. The
presence of DAX-1 protein in tumortissue was confirmed by
immunocytochemistry.
DAX-1 was demonstrated in all NFPAs, 7 of 13 somatotroph tumorsand 0
of 4 prolactinomas. SF-1 expression occurred in 8 of 16NFPAs, 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 vitrowere significantly related to the
expression of SF-1 or DAX-1.SF-1-positive somatotroph tumors
immunostained positively forLH-ß and/or FSH-ß and secreted
gonadotropinsin vitro.
SF-1 expression is associated with the in vitro
secretion ofLH by NFPAs. A proportion of somatotroph tumors
also expressSF-1 and DAX-1 and secrete gonadotropin hormones in
vitro.
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