Molecular biology of gonadotrophins

Regulation of gonadotrophin synthesis involves a complex interaction between hypothalamic and gonadal hormones. Chronic administration of oestrogens and androgens to gonadectomized animals blocked the postcastration rise in amounts of mRNA encoding gonadotrophin subunits. Removal of endogenous GnRH decreased amounts of mRNA encoding gonadotrophin subunits. Pulsatile administration of GnRH to GnRH-deficient animals increased 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 alpha subunit gene that directed expression to gonadotrophs or conferred responsiveness to oestrogens, androgens or GnRH. Unique DNA-binding proteins were also identified which directed expression of the human alpha subunit gene specifically to the pituitary. Pituitary cell lines that express bovine gonadotrophin subunit genes are 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 alpha, LH beta, or FSH beta subunit transgenes revealed that DNA sequences important for gonadotroph-specific expression and hormonal regulation resided within the proximal 5' flanking sequences.