Pretreatment of Rats with an Allosteric Luteinizing Hormone Receptor Agonist Enhances Chorionic Gonadotropin-Induced Stimulation of Testosterone Production

Abstract

In clinical practice, luteinizing hormone (LH) and chorionic gonadotropin (CG) are used as activators of the LH receptor, leading to the stimulation of gonadal steroidogenesis. However, high doses of gonadotropin preparations cause a number of side effects. Here we demonstrate that the pretreatment of male rats with TP03, an allosteric agonist of the LH receptor, at doses of 7.5–25 mg/kg significantly increases the testosterone production-stimulating effect of CG administered at a dose of 50 IU/rat, which is twice as low as that inducing a maximum steroidogenic effect. We assume that this is due to additivity of the CG and TP03 effects, as well as the potentiating effect of TP03 on CG signaling pathways. Three hours after CG administration to TP03-pretreated rats, the activation pattern of the genes of steroidogenic enzymes and LH receptor exhibits specific changes which mainly concern 3p-dehydrogenase gene expression. The obtained data indicate a prospectivity of TP03 and CG co-application allowing the effective dose of gonadotropin preparations to be reduced.