Macrophage regulation of hypothalamic-pituitary-adrenal and gonadal axis homeostasis and hormonal output

Macrophages are critical immune cells present in virtually every tissue, where they contribute to tissue homeostasis beyond their traditional immune roles. Past and recent evidence highlights their involvement in endocrine regulation, particularly within the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. This review explores the ontogeny and function of macrophages residing in the hypothalamus, pituitary, adrenals, and gonads, emphasizing their contributions to hormonal output and endocrine homeostasis. Macrophages in the hypothalamus and pituitary modulate neuroendocrine signalling, impacting stress and reproductive hormone production. In the adrenal glands, distinct macrophage subsets regulate glucocorticoid and mineralocorticoid synthesis, influencing systemic metabolism and blood pressure. Gonadal macrophages contribute to steroidogenesis and fertility, with roles in testosterone production, ovarian folliculogenesis, and corpus luteum maintenance. The emerging understanding of macrophage regulation of endocrine function may seed novel therapeutic approaches for endocrine disorders. Future research should further elucidate the molecular mechanisms underlying macrophage regulation of hormone production and explore their implications for metabolic, immune, and reproductive health.