Related Experiment Video

Updated: Aug 8, 2026

Unraveling the Role of Discrete Areas of the Rat Brain in the Regulation of Ovulation through Reversible Inactivation by Tetrodotoxin Microinjections
11:04

Unraveling the Role of Discrete Areas of the Rat Brain in the Regulation of Ovulation through Reversible Inactivation by Tetrodotoxin Microinjections

Published on: September 3, 2020

Effect of GnRH antagonists on phorbol ester-induced LH release from rat pituitary gonadotrophs

S Saito1, S Izumi, M Umeuchi

  • 1Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.

Endocrine Journal
|August 1, 1994
PubMed

Insights

Not all Gonadotropin-releasing hormone (GnRH) antagonists can block the C-kinase pathway. This study investigated three GnRH antagonists, finding that only one effectively inhibited TPA-induced LH release, challenging previous assumptions.

Area of Science:

  • Endocrinology
  • Molecular Pharmacology
  • Reproductive Biology

Background:

  • Gonadotropin-releasing hormone (GnRH) receptor activation initiates C-kinase pathways, which are crucial for luteinizing hormone (LH) release.
  • Previous findings indicated that blocking GnRH receptor activation inhibits these initiated pathways.

Purpose of the Study:

  • To determine if the inhibition of initiated C-kinase pathways by GnRH receptor blockade is a general phenomenon.
  • To evaluate the efficacy of three distinct GnRH antagonists in inhibiting GnRH-induced LH release and C-kinase pathway activation.

Main Methods:

  • Utilized three GnRH antagonists: [D-Phe2,Pro3,D-Phe6]-GnRH (#1), [Ac-D-Nal-Ala1,D-pCl-Phe2,D-Ser(Rha)6]-GnRH (#2), and [Ac-D-p-Cl-Phe1,2,D-Trp3,D-Lys6,D-Ala10]-GnRH (#3).
  • Assessed antagonist potency by measuring inhibition of LH release from pituitary gonadotrophs.
  • Monitored the effect of antagonists on cytosolic Ca2+ concentration changes.
  • Investigated the inhibitory effect on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced LH release.

Main Results:

  • GnRH antagonist #1 was less potent than #2 and #3 in inhibiting GnRH activity.
  • #3 GnRH antagonist inhibited TPA-induced LH release, consistent with prior research.
  • GnRH antagonists #2 and #3 did not inhibit TPA-induced LH release, irrespective of their potency as GnRH antagonists.

Conclusions:

  • The C-kinase pathway is vital for GnRH-induced LH release.
  • However, not all GnRH antagonists possess the ability to inhibit LH release by blocking an already activated C-kinase system.
  • The specific chemical structure of GnRH antagonists influences their ability to interfere with downstream signaling pathways beyond direct GnRH receptor antagonism.

More Related Videos

Exploring Independent Effects of Follicle-Stimulating Hormone In Vivo in a Mouse Model05:32

Exploring Independent Effects of Follicle-Stimulating Hormone In Vivo in a Mouse Model

Published on: August 11, 2023

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies06:24

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies

Published on: January 10, 2025

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Secondary Messengers in Hormone Action01:26

Secondary Messengers in Hormone Action

Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Regulation of Hormone Secretion01:19

Regulation of Hormone Secretion

Regulation of hormone secretion is a finely tuned orchestration driven by various types of stimuli, encompassing neural, humoral, and hormonal signals. Environmental cues instigate neural stimuli, where action potentials traverse nerve fibers to reach their designated targets. An illustrative scenario is the body's response to stress, wherein the sympathetic nervous system releases epinephrine from the adrenal glands, inducing the well-known 'fight or flight' reaction.
Humoral stimuli,...
Hormones of the Pituitary Gland01:27

Hormones of the Pituitary Gland

The small, pea-sized pituitary gland is located at the base of the brain. It is crucial in regulating various bodily functions, from growth to reproduction. The gland is divided into the anterior lobe and the posterior lobe. The secretory cell clusters in the pars distalis of the anterior pituitary lobe are controlled by hypothalamic regulators and synthesize six primary hormones.
The most abundantly secreted hormone from the anterior lobe is the growth hormone, which controls overall growth by...
Hormonal Regulation of the Menstrual Cycle01:22

Hormonal Regulation of the Menstrual Cycle

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 release.