Related Experiment Video

Updated: Apr 12, 2026

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies
06:24

Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies

Published on: January 10, 2025

1.7K

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism

Barbara Witek1, Abeer El Wakil1, Christoffer Nord2

  • 1Department of Molecular Biology, Umeå University, Umeå, Sweden.

Plos One
|May 9, 2015
PubMed

Insights

Anaplastic Lymphoma Kinase (ALK) plays a crucial role in male reproductive health. Loss of ALK function in mice leads to hypogonadotropic hypogonadism, impacting testosterone levels and pubertal onset.

Area of Science:

  • Reproductive Endocrinology
  • Neuroendocrinology
  • Molecular Biology

Background:

  • Anaplastic Lymphoma Kinase (ALK) is implicated in various cellular processes.
  • Previous studies noted subtle behavioral changes in ALK-deficient mice.
  • The precise role of ALK in the reproductive axis remains largely unexplored.

Purpose of the Study:

  • To investigate the role of ALK in male reproductive function.
  • To determine if ALK deficiency contributes to hypogonadotropic hypogonadism.
  • To elucidate the mechanisms underlying ALK's influence on the hypothalamic-pituitary-gonadal axis.

Main Methods:

  • Analysis of ALK knockout male mice at post-natal day 40.
  • Measurement of serum testosterone levels.
  • Histological examination of seminiferous tubules and GATA4 expression.
  • Pharmacological inhibition of ALK using crizotinib in wild-type mice.
  • Assessment of Gonadotropin-Releasing Hormone (GnRH) neuron populations in the hypothalamus.

Main Results:

  • ALK knockout males exhibited lower serum testosterone levels and disorganized seminiferous tubules with reduced GATA4 expression.
  • Chemical inhibition of ALK with crizotinib decreased testosterone levels in adult wild-type males, which normalized post-treatment.
  • A significant reduction in GnRH-positive neurons was observed in the hypothalamus of ALK knockout mice.

Conclusions:

  • ALK is essential for normal testis function and pubertal onset in male mice.
  • ALK deficiency leads to hypogonadotropic hypogonadism by affecting GnRH neuron development and function.
  • These findings highlight ALK's critical role in regulating the hypothalamic-pituitary-gonadal axis.

More Related Videos

Production of Apolipoprotein C-III Knockout Rabbits using Zinc Finger Nucleases10:59

Production of Apolipoprotein C-III Knockout Rabbits using Zinc Finger Nucleases

Published on: November 18, 2013

18.9K
Assessment of Sexual Behavior of Male Mice04:38

Assessment of Sexual Behavior of Male Mice

Published on: March 5, 2020

22.3K

Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
92
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
17.7K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
69
Sex-linked Disorders01:43

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
112.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.2K
Testosterone: Functions and Regulation01:26

Testosterone: Functions and Regulation

The intricate hormonal interplay essential for male reproductive health begins with the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus. This hormone prompts the pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH targets the Leydig cells in the testes, stimulating them to produce and release testosterone. In concert with testosterone, FSH acts on the Sertoli cells within the seminiferous tubules to facilitate the release of...
3.3K