Rapid actions of anti‐Müllerian hormone in regulating synaptic transmission and long‐term synaptic plasticity in the hippocampus

Abstract

Anti‐Müllerian hormone (Amh) is a peptide factor that is known to regulate sexual differentiation and gonadal function in mammals. Although Amh is also suggested to be associated with cognitive development and function in the postnatal brain, little is known about its expression or direct effects on neuronal activities in the hippocampus. Therefore, we assessed Amh and its receptor expression in the hippocampus of male and female mice using PCR, Western blot, and immunofluorescence staining. While Amh‐specific receptor expression was comparable between males and females, mRNA and protein levels of Amh were higher in females than those of males. Electrophysiological recordings on acute hippocampal slices showed that exogenous Amh protein addition increased synaptic transmission and long‐term synaptic plasticity at the Cornu Ammonis (CA) 3‐CA1 synapses. Amh exposure also increased the excitatory postsynaptic potential at CA1 synapses. Our findings support direct and rapid actions of Amh as a paracrine and/or autocrine factor in regulating hippocampal neuronal activities. Data provide functional evidence of Amh‐mediated postsynaptic modulation of synaptic transmission and Amh‐regulated long‐term synaptic plasticity in the hippocampus. These results suggest a potential role of Amh in learning and memory, and a possible cause of the sex differences in cognitive development and function.

New insights into anti-Müllerian hormone role in the hypothalamic–pituitary–gonadal axis and neuroendocrine development

“…It has been reported that adult motor neurons secrete and respond to AMH in an autocrine/paracrine manner in the central nervous system of mice [ 29 ]. In addition, adult neurons in the forebrain produce AMH and effectively respond to AMH actions changing their electrical behavior, such as increasing synaptic potentiation in hippocampal neurons [ 30 ]. Therefore, different levels of circulating AMH throughout development and adult life, as well as different levels of tissular expression of AMH and AMH receptors may define the impact of AMH signaling in reproductive and non-reproductive tissues.…”

“…In line with this notion, some recent findings started to shed light on the possible role of AMH locally produced in the brain in the modulation of neuronal activity, i.e. in the hippocampus [ 30 ]. Since AMH levels were reported to be higher in the plasma of adult female mice but not in the cerebrospinal fluid (CSF) as compared to males [ 30 ], it is possible to speculate that certain neuronal populations, like hippocampal neurons or GnRH neurons, produce AMH which, if secreted, could enter the CSF and potentially act as a paracrine factor via the CSF circulation in regulating functions of other brain structures, including the hypothalamus, which is known to express AMHR2 [ 6 ].…”

Pathophysiological Bases for the Classification of the Human Sex Development Anomalies

“…After puberty, T, aided by meiotic germ cells, suppresses AMH secretion in males, and therefore subjects with androgen insensitivity syndrome (androgen receptor defects) have very high levels of AMH after puberty. The effects of AMH on neural activities in the hippocampus have also been studied, suggesting a potential role in learning and memory, and a possible cause of sex differences in cognitive development and function [23].…”

Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers

“…Twenty-four hours post plating, cells were treated with 0 (control) or 5 nM calcitriol (biologically active form of VD; Sigma-Aldrich) supplementation in the culture medium for 72 hrs. Cells were harvested for Western blot, as previously described [50]. Briefly, total protein was extracted using a RIPA buffer containing 150 mM NaCl, 1% (v/v) NP-40, 1% (w/v) sodium deoxycholate, 0.1% (w/v) SDS, and 25 mM Tris-HCl (pH 7.6), electrophoresed on 4-12% Bis-Tris gel, and transferred to a nitrocellulose membrane.…”