Oxytocin and Steroid Actions

Abstract

Biosynthesis and secretion of the hypothalamic nonapeptide oxytocin largely depends on steroid hormones. Estradiol, corticosterone, and vitamin D seem to be the most prominent actors. Due to their lipophilic nature, systemic steroids are thought to be capable of crossing the blood-brain barrier, thus mediating central functions including neuroendocrine and behavioral control. The actual mode of action of steroids in hypothalamic circuitry is still unknown: Most of the oxytocinergic perikarya lack nuclear steroid receptors but express proteins suspected to be membrane receptors for steroids. Oxytocin expressing neurons contain enzymes important for intrinsic steroid metabolism. Furthermore, they produce and probably liberate specific steroid-binding globulins. Rapid responses to steroid hormones may involve these binding proteins and membrane-associated receptors, rather than classic nuclear receptors and genomic pathways. Neuroendocrine regulation, reproductive behaviors, and stress response seem to depend on these mechanisms.

Is Oxytocin “Nature’s Medicine”?

“…2). Furthermore, there is evidence, especially in the face of psychologic or physical challenges, that males and females may differ in their response to oxytocin and vasopressin (Carter and Perkeybile, 2018;Jirikowski et al, 2018).…”

“…Use of drugs, such as opiates, stimulants, and selective serotonin reuptake inhibitors, and diet, can affect both endogenous oxytocin and its receptors with effects that are largely unknown. In addition, sex differences in oxytocin and vasopressin are common, and it is likely that steroids, including estrogens, androgens (Carter and Perkeybile, 2018;Jirikowski et al, 2018), and glucocorticoids (Liberzon and Young, 1997), play a major role in the regulation of the actions of oxytocin and availability of receptors for oxytocin across the lifecycle. As described below, stress and experiences across the life cycle also have major consequences for the release and actions of oxytocin and vasopressin.…”

“…Because of the adaptive nature of these hormonal systems and the fact that sexual differentiation is influenced by genetics, epigenetics, and physiologic processes (including inflammation) across the lifespan (McCarthy et al, 2017), the relationship between sex and peptides is not very well-understood. Steroids, including estrogen and testosterone of either endogenous or exogenous origins, can influence both oxytocin and vasopressin as well as the expression of their receptors (Jirikowski et al, 2018). The study of sex differences in oxytocin and vasopressin is further complicated by dynamic changes in steroids that are experienced in both sexes across the lifecycle.…”

On the Nature of the Mother-Infant Tie and Its Interaction With Freudian Drives

“…Of course, a variety of signal molecules modulate oxytocin secretion [for instance caffeine results in the release of oxytocin (Wu et al, 2017)], but in this manuscript the search for such chemical messengers must be restricted to imperative motor factors. Although hypothalamic biosynthesis of oxytocin depends on the intermediacy of estrogens like estradiol (i.e., a downstreaming product of testosterone), most of the oxytocinergic neurons do not express a receptor for this steroid hormone on their surfaces (Jirikowski et al, 2018) and because of this missing target an efficient release of oxytocin induced by estradiol is unlikely 22 . Thus, estradiol is involved in the biosynthesis of oxytocin and in the optimization of oxytocin receptors but estradiol is of minor importance for the oxytocin release.…”

“…Noticeably, enhanced ghrelin levels are present in human infants and in their mothers' breast milk (Savino et al, 2011;Shilina et al, 2011;Kon et al, 2014). Secondly, oxytocin decreases ghrelin levels in healthy males (Vila et al, 2009), promote termination of feeding in untrained animals (Arletti et al, 1989;Herisson et al, 2016;Head et al, 2019) and can 22 There are multiple evidences that estradiol increases the density of oxytocin receptors in the brain and enhances the affinity of oxytocin to its corresponding receptors (Jirikowski et al, 2018). 23 Oxytocin is metabolized by various oxytocinases present in synaptic brain membranes (Stancampiano et al, 1991).…”