非従来のエンドカンナビノイド信号は,性ホルモンプロゲステロンによる精子活性化を制御する

Melissa R Miller¹, Nadja Mannowetz¹, Anthony T Iavarone²

¹Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

Science (New York, N.Y.)

|March 19, 2016

まとめ

プロゲステロンは新しい経路で精子の活性化を誘発します酵素ABHD2はエンドカンナビノイドを枯渇させ,受精に不可欠なカルシウム流入を可能にします.

科学分野:

生殖生物学
分子内分泌学
生物化学

背景:

ステロイドは核およびゲノム独立経路を通じて細胞機能を媒介する.
ゲノム独立のシグナリングは精子の活性化と卵子の成熟を制御しますが,重要な分子プレーヤーは不明です.

研究の目的:

ゲノム独立のシグナル伝達に関与するヒト精子のプロゲステロン受容体の特徴を明らかにする.
プロゲステロンによる精子活性化のメカニズムを解明する.

主な方法:

ヒト精子における孤児酵素アルファ/ベータヒドロラーゼドメイン含有タンパク質2 (ABHD2) の特徴
ABHD2の酵素活性とプロゲステロン結合の測定
エンドカンナビノイドレベルと精子のカルシウム流入の測定

主要な成果:

ABHD2は精子の中で高度に発現し,プロゲステロンと結合する.
ABHD2はプロゲステロン依存性脂質ヒドローラーゼとして機能し,2- アラキドノイルグリセロール (2AG) を血から排出する.
2AGがABHD2によって枯渇すると,CatSper経路を通るカルシウム流入が促進され,精子の活性化につながります.

結論:

ゲノム独立のステロイド作用の鍵となるメカニズムは,ABHD2によるプロゲステロン活性化エンドカンナビノイド減少である.
この経路はカルシウム信号を調節することで精子を受精させる準備をします
ABHD2は男性の生育能力を理解し,潜在的に調節するための新しいターゲットです.

さらに関連する動画

10:02

Two Types of Assays for Detecting Frog Sperm Chemoattraction

Published on: December 27, 2011

19.7K

08:50

Prostaglandin Extraction and Analysis in Caenorhabditis elegans

Published on: June 25, 2013

20.2K

関連する概念動画

01:27

Feedback Regulation of Calcium Concentration

4.2K

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...

4.2K

01:08

Chemical Signaling in the Endocrine System

7.9K

A signaling cascade is a series of events that facilitates the transmission of information within or between cells, culminating in a targeted response in the recipient cell. As chemical messengers, hormones are pivotal in initiating and modulating these intricate signaling cascades based on their solubility.
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...

7.9K

01:22

Hormonal Regulation of the Menstrual Cycle

2.2K

The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...

2.2K

01:45

Endocrine Signaling

69.2K

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.

Endocrine Signaling

Spermatogenesis

Spermatogenesis is the process by which haploid sperm cells are produced in the male testes. It starts with stem cells located close to the outer rim of seminiferous tubules. These spermatogonial stem cells divide asymmetrically to give rise to additional stem cells (meaning that these structures “self-renew”), as well as sperm progenitors, called spermatocytes. Importantly, this method of asymmetric mitotic division maintains a population of spermatogonial stem cells in the male...