Endocrine Abstracts

Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for activating and maintaining the function of the hypothalamic-pituitary-gonadal (HPG) axis, which controls the onset of puberty and fertility. Two provocative recent studies [1,2] suggest that, in addition to controlling reproduction, the neurons in the brain that produce GnRH are also involved in the control of postnatal brain maturation, odor discrimination, and adult cognition. I will discuss the development and establishment of the GnRH system, and especially the importance of its first postnatal activation, a phenomenon known as minipuberty, to its later functions, reproductive and non-reproductive. In addition, I will discuss the beneficial effects of restoring physiological, i.e. pulsatile, GnRH levels on olfactory and cognitive alterations in Down syndrome and preclinical models of Alzheimer’s disease, as well as the risks associated with long-term continuous, i.e. non-physiological, GnRH administration in certain disorders [3]. Finally, I’ll discuss the intriguing possibility that pulsatile GnRH therapy may hold therapeutic potential for the management of some neurodevelopmental cognitive disorders as well as pathological aging in the elderly. This work was supported by National Grant no. ANR-17-CE16-0015 (GRAND), ANR-11-LABEX-0009 (DistAlz) and ANR-16-IDEX-0004 (I-SITE ULNE), and European Grant no. 101123221 (ERC-2023-PoC UPGRADE).

References: 1. Manfredi-Lozano et al., Science, 377, eabq4515 (2022). PMID: 36048943. 2. Chachlaki et al., Sci Transl Med, 14, eabh2369 (2022). PMID: 36197968. 3. Prevot et al., J Clin Endocrinol Metab, 108, 2747-2758 (2022). PMID: 37261390.