Hypothalamic but Not Pituitary or Ovarian Defects Underlie the Reproductive Abnormalities in Axl/Tyro3 Null Mice

Overview

Journal Mol Cell Endocrinol

Specialties Cell Biology
Endocrinology
Molecular Biology

Date 2011 May 5

PMID 21539887

Citations 16

Authors

Angela Pierce

Mei Xu

Brian Bliesner

Zhilin Liu

Joanne Richards

Stuart Tobet

Margaret E Wierman

Affiliations

Soon will be listed here.

Abstract

AXL and TYRO3, members of the TYRO3, AXL and MER (TAM) family of tyrosine kinase receptors, modulate GnRH neuronal cell migration, survival and gene expression. Axl/Tyro3 null mice exhibit a selective loss of GnRH neurons, delayed sexual maturation and irregular estrous cycles. Here we determined whether the defects were due to direct ovarian defects, altered pituitary sensitivity to GnRH and/or an impaired LH surge mechanism. Ovarian histology and markers of folliculogenesis and atresia as well as corpora luteal development and ovarian response to superovulation were not impaired. Axl/Tryo3 null mice exhibited a robust LH response to exogenous GnRH, suggesting no altered pituitary sensitivity. Ovariectomized Axl/Tyro3 null mice, however, demonstrated an impaired ability to mount a steroid-induced LH surge. Loss of GnRH neurons in Axl/Tyro3 null mice impairs the sex hormone-induced gonadotropin surge resulting in estrous cycle abnormalities confirming that TAM family members contribute to normal female reproductive function.

Citing Articles

AXL receptor tyrosine kinase modulates gonadotropin-releasing hormone receptor signaling.

Mohammadzadeh P, Roueinfar M, Amberg G Cell Commun Signal. 2023; 21(1):284.

PMID: 37828510 PMC: 10568877. DOI: 10.1186/s12964-023-01313-y.

AXL/Gas6 signaling mechanisms in the hypothalamic-pituitary-gonadal axis.

Mohammadzadeh P, Amberg G Front Endocrinol (Lausanne). 2023; 14:1212104.

PMID: 37396176 PMC: 10310921. DOI: 10.3389/fendo.2023.1212104.

TAM Signaling in the Nervous System.

Burstyn-Cohen T, Hochberg A Brain Plast. 2021; 7(1):33-46.

PMID: 34631419 PMC: 8461745. DOI: 10.3233/BPL-210125.

Tumour-Secreted Protein S (ProS1) Activates a Tyro3-Erk Signalling Axis and Protects Cancer Cells from Apoptosis.

Al Kafri N, Hafizi S Cancers (Basel). 2019; 11(12).

PMID: 31766614 PMC: 6966665. DOI: 10.3390/cancers11121843.

The Emerging Role of TYRO3 as a Therapeutic Target in Cancer.

Smart S, Vasileiadi E, Wang X, DeRyckere D, Graham D Cancers (Basel). 2018; 10(12).

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