MOLECULAR-BIOLOGY OF GONADOTROPINS

Regulation of gonadotrophin synthesis involves a complex interaction b etween hypothalamic and gonadal hormones. Chronic administration of oe strogens and androgens to gonadectomized animals blocked the postcastr ation rise in amounts of mRNA encoding gonadotrophin subunits. Removal of endogenous GnRH decreased amounts of mRNA encoding gonadotrophin s ubunits. Pulsatile administration of GnRH to GnRH-deficient animals in creased amounts of mRNA encoding gonadotrophin subunits. Studies using transgenic mice and transient transfection assays identified at least eight cis-acting DNA sequences in the proximal 350 bp of 5' flanking sequence of the human ct subunit gene that directed expression to gona dotrophs or conferred responsiveness to oestrogens, androgens or GnRH. Unique DNA-binding proteins were also identified which directed expre ssion of the human alpha subunit gene specifically to the pituitary. P ituitary cell lines that express bovine gonadotrophin subunit genes ar e not currently available; thus, relatively little is known about the molecular mechanisms that regulate expression of bovine gonadotrophin subunit genes. Recent studies with transgenic mice harbouring bovine a lpha, LH beta, or FSH beta subunit transgenes revealed that DNA sequen ces important for gonadotroph-specific expression and hormonal regulat ion resided within the proximal 5' flanking sequences.