We are also exploring the non-traditional effects of oxytocin (OXT), which is produced by hypothalamic nuclei and secreted by the neurohypophysis into the circulation. While OXT primarily regulates parturition and lactation in mammals, it also interacts with oxytocin receptors in various brain regions and somatic organs, including the adrenal gland and adipose tissue. The adreno-medullary system, crucial for responding to stress, is influenced by OXT. Activated by various stress stimuli, oxytocin neurons release OXT, modulating stress responses, particularly in females.

PCOS Phenotypes Across Diverse Populations

The program aims to understand the phenotypes of disorders associated with LH dysfunction, such as PCOS, across diverse age groups, ethnic backgrounds, and referral types from clinical settings to general populations around the globe. The approach uses epidemiological data, systematic reviews, and meta-analysis techniques.

LH and Body Composition

This program is investigating how LH influences body fat distribution and energy metabolism. We have demonstrated abundant LH/choriogonadotropin receptor (LHCGR) expression on adipocytes within both mouse and human fat deposits and characterized the expression and activity of these receptors. These novel data show that activating the LH receptor in adipocytes can prevent obesity by increasing energy expenditure and reducing fat accumulation, suggesting a new strategy for treating metabolic disorders.

Therapeutic Development

Leveraging the therapeutic potential of LHCGR, the program is implementing novel small molecule therapeutics to target this receptor. These compounds aim to prevent obesity by modulating adipocyte function, independent of traditional appetite-suppression mechanisms.

LH and Mood Regulation

In collaboration with the Neurohormone Program, our researchers, led by Director Vitaly Ryu, PhD, have quantified LH receptors in various brain regions, potentially impacting cognitive functions and emotional health. These in vivo data indicate that the loss of LH signaling in genetically modified models reverses age-related emotional disturbances, setting the stage for future studies on the direct effects of LH on mood-related disorders and cognitive function.

Oxytocin and the Hypothalamic-Pituitary-Adrenalin Axis

Our current research focuses on the interactions between the effects of OXT and the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, especially in terms of stress responses. Led by Anisa Gumerova, MD, PhD, the group has studied OXT receptor expression in mice, analyzing variations by gender and age within components of the HPA axis. Additionally, they have developed a tissue-specific OXT receptor knock-out model targeting steroidogenic tissues, such as the adrenal cortex, to elucidate the role of oxytocin in regulating adrenal function during stress. This research is poised to facilitate the development of novel avenues for understanding stress regulation.