Hypophysial angiogenesis decodes annual time and underlies physiological adaptation to seasonal changes in the environment

Abstract

Adaptation to annual changes in the environment is controlled by hypophysial hormones. In temperate zones, photoperiod is the primary external cue that regulates annual biological cycles and is translated by the pattern of melatonin secretion acting primarily in the hypophysial pars tuberalis. Angiogenic mechanisms within this tissue contribute to decode the melatonin signal through alternative splicing of the vascular endothelial growth factor A (VEGF-A) gene in both the pars tuberalis and the capillary loops of the infundibulum. The resulting melatonin-evoked differential productions of VEGF-A isoforms will induce seasonal remodeling of the vascular connection between the hypothalamus and hypophysis, and act as paracrine messengers in the pars distalis to generate the required seasonal endocrine response. Specifically, the long melatonin signal in winter upregulates antiangiogenic VEGF-A isoforms, which will reduce the number of vascular loops and the density of VEGF receptors in endocrine and folliculo-stellate (FS) cells, inhibit prolactin secretion, and stimulate FSH. In contrast, the short melatonin signal in summer upregulates proangiogenic VEGF-A isoforms that will increase the number of vascular loops and the density of VEGF receptors in endocrine and FS cells, stimulate prolactin secretion, and suppress FSH. A similar system has been identified in long day seasonal breeders, revealing that this is a conserved mechanism of adaptation across species. Thus, an angiogenesis-based, intrahypophysial system for annual time measurement controls local microvascular plasticity and conveys the photoperiodic signal readout from the melatonin sensitive pars tuberalis to the endocrine cells of the pars distalis to regulate seasonal adaptation to the environment.

An introduction to the Special Issue on seasonal rhythms in birds and mammals

“…Annual changes in localized blood availability achieved via angiogenesis in the testes was proposed to be a major contributor to seasonal changes in testes growth and involution (Young & Nelson, 2000). Recent findings outlined by Tortonese indicates that melatonin also impacts angiogenesis in the pituitary and suggest that hormone‐driven changes in vascular endothelial growth factor isoforms are a critical step in the photoperiodic timing of reproduction in sheep (Tortonese, 2022). Finally, lactotrophs were previously established as circannual timers in sheep (Lincoln et al, 2006).…”