Actions Of Pituitary Hormones Beyond Traditional Targets

[Michael Scally MD]

[OA] Actions Of Pituitary Hormones Beyond Traditional Targets

Studies over the past decade have challenged the long-held belief that pituitary hormones have singular functions in regulating specific target tissues, including master hormone secretion.

Our discovery of the action of thyroid-stimulating hormone (TSH) on bone provided the first glimpse into the non-traditional functions of pituitary hormones.

Here we discuss evolving experimental and clinical evidence that growth hormone (GH), follicle-stimulating hormone (FSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine vasopressin (AVP) regulate bone and other target tissues, such as fat.

Notably, genetic and pharmacologic FSH suppression increases bone mass and reduces body fat, laying the framework for targeting the FSH axis for treating obesity and osteoporosis simultaneously with a single agent.

Certain ‘pituitary’ hormones, such as TSH and oxytocin, are also expressed in bone cells, providing local paracrine and autocrine networks for the regulation of bone mass.

Overall, the continuing identification of new roles for pituitary hormones in biology provides an entirely new layer of physiologic circuitry, while unmasking new therapeutic targets.

Zaidi M, New MI, Blair HC, et al. Actions of pituitary hormones beyond traditional targets. Journal of Endocrinology 2018;237:R83-R98. http://joe.endocrinology-journals.org/content/237/3/R83.abstract

 

[Michael Scally MD]

Mouse Models for The Analysis of Gonadotropin Secretion and Action

Gonadotropins are pituitary gonadotrope-derived glycoprotein hormones. They act by binding to G-protein coupled receptors on gonads. Gonadotropins play critical roles in reproduction by regulating both gametogenesis and steroidogenesis.

Although biochemical and physiological studies provided a wealth of knowledge, gene manipulation techniques using novel mouse models gave new insights into gonadotropin synthesis, secretion and action.

Both gain of function and loss of function mouse models for understanding gonadotropin action in a whole animal context have already been generated.

Moreover, recent studies on gonadotropin actions in non-gonadal tissues challenged the central dogma of classical gonadotropin actions in gonads and revealed new signaling pathways in these non-gonadal tissues.

In this Chapter, we have discussed our current understanding of gonadotropin synthesis, secretion and action using a variety of genetically engineered mouse models.

Gilbert SB, Roof AK, Rajendra Kumar T. Mouse models for the analysis of gonadotropin secretion and action. Best Practice & Research Clinical Endocrinology & Metabolism 2018;32:219-39. http://www.sciencedirect.com/science/article/pii/S1521690X18300484