Recent advances in understanding gonadotropin signaling

Gonadotropins are glycoprotein sex hormones regulating development and reproduction and bind to specific G protein–coupled receptors expressed in the gonads. Their effects on multiple signaling cascades and intracellular events have recently been characterized using novel technological and scientific tools. The impact of allosteric modulators on gonadotropin signaling, the role of sugars linked to the hormone backbone, the detection of endosomal compartments supporting signaling modules, and the dissection of different effects mediated by these molecules are areas that have advanced significantly in the last decade. The classic view providing the exclusive activation of the cAMP/protein kinase A (PKA) and the steroidogenic pathway by these hormones has been expanded with the addition of novel signaling cascades as determined by high-resolution imaging techniques. These new findings provided new potential therapeutic applications. Despite these improvements, unanswered issues of gonadotropin physiology, such as the intrinsic pro-apoptotic potential to these hormones, the existence of receptors assembled as heteromers, and their expression in extragonadal tissues, remain to be studied. Elucidating these issues is a challenge for future research.