Vasopressin and Oxytocin Neurons of the Human Supraoptic and Paraventricular Nucleus; Size Changes in Relation to Age and Sex

Abstract

The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei consist of arginine vasopressin (AVP)- and oxytocin (OT)-synthesizing neurons that send projections to the neurohypophysis, whereas the PVN also projects to other brain areas. A growing body of evidence in animals suggests the presence of sex differences in the vasopressinergic and oxytocinergic systems. The present study was aimed at determining whether the sizes of AVP and OT neurons in the human SON and PVN show sex differences, as earlier studies demonstrated that a change in neuronal size is a sensitive parameter for activity. The minimal and maximal diameters were determined to estimate the volumes of cell somata and cell nuclei in AVP and OT neurons stained with an antibody against human glycoprotein-(22-39), a part of the AVP precursor, and a monoclonal anti-OT antibody in 15 men and 17 women ranging in age from 29-94 yr. The AVP neurons appeared to be larger in young men than in young women (< or =50 yr old). In elderly women (>50 yr old) AVP cell size considerably exceeded that in young women. In elderly men AVP neurons were larger than in young men and elderly women, although these differences were not significant. In addition, AVP cell size correlated positively with age in women but not in men. No significant differences were found in the AVP cell nucleus volumes among all four groups studied. Sex differences in the size of the PVN vasopressin neurons were pronounced at the left side (P = 0.048) and absent at the right side (P = 0.368), indicating the presence of functional lateralization in this nucleus. No difference was found in any morphometric parameter of OT neurons in the PVN among the 4 groups studied. Thus, our data demonstrate sex differences in the size of the AVP neurons, and thus in their function, that are age and probably also side dependent and the absence of such changes in OT neurons in the PVN. These data provide a basis for the reported higher AVP plasma levels in men compared to women.

Alteration in Anxiety with Relation to the Volume of the Locus Ceruleus in Progranulin-Deficient Mice

“…These inconsistent results may be attributable to differences between species in anxiety-like behavior. It is worth noting that hybrid strains of C57BL/6J and 129 mice show sexual differences in anxiety during OFT [24], which is consistent with the results of our studies (i.e., higher anxiety in females than males), although many reports in rats suggest inverse relationships between sexes and anxiety (i.e., higher anxiety in males than females).The PVN is a nucleus showing sexual dimorphism, where estrogens secreted after sexual maturation are thought to influence the volume of neuronal cell bodies [17]. Located in the anterior hypothalamus, the PVN plays a critical role in the hypothalamicpituitary-adrenal axis, and this physiological cascade is also influenced by sex steroids [25].…”

“…The PVN is a nucleus showing sexual dimorphism, where estrogens secreted after sexual maturation are thought to influence the volume of neuronal cell bodies [17]. Located in the anterior hypothalamus, the PVN plays a critical role in the hypothalamicpituitary-adrenal axis, and this physiological cascade is also influenced by sex steroids [25].…”

“…First, we confirmed the disappearance of sex differences in anxiety in pgrn -/-mice and examined whether castration and/or testosterone treatment affects this behavior. Next, we measured the volumes of the paraventricular nucleus (PVN) and the locus ceruleus (LC), as these are anxiety/stress-related nuclei known to have sex differences in their structures [17,18]. …”

Sexual Diergism of Hypothalamo-Pituitary–Adrenal Cortical Responses to Low-Dose Physotigmine in Elderly vs. Young Women and Men

“…AVP-producing neurons in the human supraoptic (SON) and paraventricular (PVN) nuclei remain intact in old age (Hofman 1997), and both may contribute to HPA axis regulation (Holmes et al 1986;Antoni et al 1990). As well, CRH neurons increase in the human PVN with age (Raadsheer et al 1994), there is an age-dependent colocalization of CRH and AVP in the human PVN (Raadsheer et al 1993), and larger AVP neurons have been found in the PVN of elderly men compared with those in elderly women (Ishunina and Swaab 1999). These findings suggest that AVP may play a more important role in the regulation of the HPA axis in elderly versus young subjects and in elderly men versus elderly women, consistent with the magnitude of the AVP:ACTH correlations in our elderly and young men.…”

Study of neurogenic involvement in arginine-vasopressin and oxytocin release under basal and environmentally stimulated conditions

“…1). Smaller amounts of OXT are also detectable in the SON [19,38]. The OXT-ergic trajectories innervate various extrahypothalmic targets [5].…”