Brain Circuits for Hormonal Control: Sex differences and ageing in growth hormone regulation (360G-Wellcome-333003_Z_25_Z)

Pulsatile growth hormone (GH) secretion is essential for growth, metabolism, and tissue maintenance. These pulse patterns are influenced by sex, age, and hormonal feedback, yet the neural circuits remain poorly defined. This research aims to establish a mechanistic framework for how hypothalamic GH- releasing hormone (GHRH) and somatostatin (SST) neurons generate and regulate sex- and age-specific GH pulses. Using in-vivo tools including fibre photometry, optogenetics, chemogenetics, and miniscopes, we will record and manipulate GHRH and SST neuron activity, examining how they encode GH pulses and how their activity is shaped by hormonal feedback and sex steroids across the lifespan. Preliminary data reveal sex-specific GHRH neuron dynamics and demonstrate feasibility of these approaches. In later stages, we will investigate non-canonical roles of GHRH neurons beyond pituitary regulation. GHRH neurons also appear in the zona incerta (ZI), a region implicated in arousal and cognitive flexibility, where they may serve distinct functions from their hypothalamic counterparts. Using viral tracing, gene expression, and neural manipulation, we will map their connectivity and test roles in memory and cognition. This work will broaden the conceptual scope of neural control of growth hormone and behaviour and lay a foundation for future sex- and age-informed strategies targeting hormonal dysregulation.