The relationship between steroidogenic factor 1 and DAX-1 expression and in vitro gonadotropin secretion in human pituitary adenomas

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-beta and glycoprotein hormone alpha -subunit (alpha GSU) gene promo ters. Pituitary adenomas from 34 patients [13 somatotroph tumors, 4 prolact inomas, and 17 clinically nonfunctioning pituitary adenomas (NFPAs)] were e nzymatically dispersed and cultured in vitro for 48 h. Tissue culture mediu m was collected and assayed for LH, FSH, and alpha GSU; messenger RNA was e xtracted from adherent cells, and expression of SF-1 and DAX-1 messenger RN A was determined by RT-PCR and verified by direct DNA sequencing. The prese nce 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 somatotro ph tumors, and 1 of 4 prolactinomas. LH secretion in vitro was greater in N FPAs that were SF-1 positive (P < 0.05). Neither FSH secretion nor <alpha>G SU secretion in vitro were significantly related to the expression of SF-1 or DAX-1. SF-1-positive somatotroph tumors immunostained positively for LH- beta and/or FSH-beta 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 g onadotropin hormones in vitro.