A MECHANISM FOR THE DIFFERENTIAL REGULATION OF GONADOTROPIN SUBUNIT GENE-EXPRESSION BY GONADOTROPIN-RELEASING-HORMONE

The hypothalamic hormone gonadotropin-releasing hormone (GnRH) is rele ased in a pulsatile fashion, with its frequency varying throughout the reproductive cycle. Varying pulse frequencies and amplitudes differen tially regulate the biosynthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by pituitary gonadotropes, The mechanism by which this occurs remains a major question in reprod uctive physiology. Previous studies have been limited by the lack of a vailable cell lines that express the LH and FSH subunit genes and resp ond to GnRH, We have overcome this limitation by transfecting the rat pituitary GH(3) cell line with rat GnRH receptor (GnRHR) cDNA driven b y a heterologous promoter, These cells, when cotransfected with regula tory regions of the common alpha, LH beta, or FSH beta subunit gene fu sed to a luciferase reporter gene, respond to GnRH with an increase in luciferase activity, Using this model,,ve demonstrate that different cell surface densities of the GnRHR result in the differential regulat ion of LH and FSH subunit gene expression by GnRH. This suggests that the differential regulation of gonadotropin subunit gene expression by GnRH observed in vivo in rats may, in turn, be mediated by varying go nadotrope fell surface GnRHR concentrations, This provides a physiolog ic mechanism by which a single ligand can act through a single recepto r to regulate differentially the production of two hormones in the sam e cell.