Differential regulation of rat luteinizing hormone alpha- and beta-subunits during the stimulatory and down-regulatory phases of gonadotropin-releasing hormone action.

Chronic treatment with agonist analogs of GnRH or long term continuous administration of GnRH results in down-regulation of pituitary LH secretion. We investigated the changes in the LH subunits during the stimulatory and down-regulatory phases of GnRH action in rat pituitary cell monolayer culture. The rat pituitary cells in culture, pretreated with medium alone or GnRH agonist for 48 h, were incubated with graded doses of GnRH for 4 h, and LH, LH alpha, and LH beta concentrations in the media and cell pellets were measured by specific and sensitive RIAs. Cells pretreated with medium alone responded to GnRH with a dose-dependent increase in LH, LH alpha, and LH beta immunoreactivity in the medium. However, rat LH, LH alpha, and LH beta concentrations in the cell pellets showed a dose-dependent decrease with GnRH treatment. Pretreatment with GnRH agonist led to a marked decrease in the LH response of cells to graded doses of GnRH. During this down-regulatory phase, the concentrations of LH beta in the medium remained undetectable even though LH alpha immunoreactivity remained persistently and disproportionately elevated. These data suggest that the alpha- and beta-subunits of rat LH are both coordinately and differentially regulated. During the stimulatory phase of GnRH action, both subunits rise concordantly, but during the down-regulatory phase the secretion of the two subunits becomes unbalanced. The changes in the beta-subunit closely parallel the changes in the concentrations of LH dimer, pointing to the key role of beta-subunit in regulation of LH secretion.