Endocrine Abstracts

Bone morphogenetic proteins (BMPs) regulate growth, differentiation and apoptosis in a variety of tissues and have crucial roles in the regulation of reproduction. BMPs bind specific Type II receptors and form complexes with Type I receptors (Alk2, 3 or 6) whereby the Type II receptors activate Type I receptors by phosphorylation. BMP2 and 4 play a crucial role in the development of the gonadotroph cell lineage during mouse pituitary morphogenesis and BMP6, 7, and 15 stimulate FSH production in rat pituitary gonadotrophs. The majority of nonfunctioning pituitary adenomas (NFPAs) are poorly differentiated gonadotrophinomas with low functional activity. They show preferential expression or secretion of FSH over LH, implying a defect in regulation of FSH. We have investigated the expression of BMP receptors in human pituitary adenomas. Pituitary adenomas obtained (with approval from the Local Ethics Committee) from 30 patients (8 somatotroph tumours, 4 corticotroph tumours and 18 NFPAs) were cultured in vitro for 24 hours. Culture medium was collected and assayed for LH, FSH and alphaGSU; messenger RNA was extracted from adherent cells, and expression of Alk2, Alk3, Alk6, and Type II receptor messenger RNA was determined by RT-PCR. PCR products were verified by direct DNA sequencing. Type II receptor was demonstrated in 72% of NFPAs, 63% of somatotroph tumours and only one corticotroph tumour. ALK3 expression occurred in 50% of NFPAs, 38% of somatotroph tumours and one corticotroph tumour. Co-expression of Type II and ALK3 receptor was found in 6 NFPAs and 3 somatotroph adenomas. ALK2 expression was not found in any tumour studied and ALK6 expression only occurred in 2 tumours. Neither Type II nor ALK3 receptor expression was significantly related to LH, FSH or alphaGSU secretion in vitro. Thus, differential expression of BMP receptors occurs in human pituitary adenomas, although this does not appear to relate to observed FSH production from tumour cells cultured in vitro.

Funded by Bart's Cancer Research Committee.