Effect of oestrogen-dependent vasopressin on HPA axis in the median eminence of female rats

Kazuaki Nishimura,Yoichi Ueta,Hiromichi Ueno,Mitsuhiro Yoshimura,Hiroki Beppu,Yasuki Akiyama,Kentaro Tanaka,Kiyoshi Yoshino,Hitoshi Ozawa,Haruki Nishimura,Kenya Sanada,Takashi Maruyama,Satomi Sonoda

doi:10.1038/s41598-019-41714-z

Abstract

The median eminence (ME) anatomically consists of external (eME) and internal (iME) layers. The hypothalamic neurosecretory cells terminate their axons in the eME and secrete their neurohormones regulating anterior pituitary hormone secretion involved in stress responses into the portal vein located in the eME. Magnocellular neurosecretory cells (MNCs) which produce arginine vasopressin (AVP) and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON) terminate their axons in the posterior pituitary gland (PP) through the iME. Here, we provide the first evidence that oestrogen modulates the dynamic changes in AVP levels in the eME axon terminals in female rats, using AVP-eGFP and AVP-DREADDs transgenic rats. Strong AVP-eGFP fluorescence in the eME was observed at all oestrus cycle stages in adult female rats but not in male transgenic rats. AVP-eGFP fluorescence in the eME was depleted after bilateral ovariectomy but re-appeared with high-dose 17β-oestradiol. AVP-eGFP fluorescence in the MNCs and PP did not change significantly in most treatments. Peripheral clozapine-N-oxide administration induced AVP-DREADDs neurone activation, causing a significant increase in plasma corticosterone levels in the transgenic rats. These results suggest that stress-induced activation of the hypothalamic-pituitary-adrenal axis may be caused by oestrogen-dependent upregulation of AVP in the eME of female rats.

Highlights

The magnocellular neurosecretory cells (MNCs) which synthesise arginine vasopressin (AVP) and oxytocin (OXT) in the paraventricular (PVN) and supraoptic nuclei (SON) project their axons through the internal layer of the median eminence to terminations in the posterior pituitary gland (PP), from which AVP is secreted into systemic circulation[1]
AVP-enhanced green fluorescent protein (eGFP) fluorescence in the eME is stronger in females than males
The locations of the SON, magnocellular division of the PVN, parvocellular division of the PVN, and median eminence (ME) were determined according to the coordinates www.nature.com/scientificreports in the rat brain atlas of Paxinos and Watson[16]

Summary

Introduction

The magnocellular neurosecretory cells (MNCs) which synthesise arginine vasopressin (AVP) and oxytocin (OXT) in the paraventricular (PVN) and supraoptic nuclei (SON) project their axons through the internal layer of the median eminence (iME) to terminations in the posterior pituitary gland (PP), from which AVP is secreted into systemic circulation[1]. AVP- and corticotrophin-releasing hormone (CRH)-containing neurones in the parvocellular neurosecretory cells (PNCs) of the PVN project their axons into the external layer of the ME (eME), from which the neurohormones are secreted into pituitary portal circulation[2,3]. Both AVP and CRH are known to stimulate adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland and corticosterone (cortisol) secretion from the adrenal gland[4,5]. It was used to stimulate hypothalamic AVP neurones and investigate the function of AVP

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