Protein tyrosine phosphatase receptors N and N2 regulate gonadotropin-releasing hormone neuron function
2023
Authors:
Sokanović, SrđanConstantin, Stephanie
Lamarca Dams, Aloa
Mochimaru, Yuta
Smiljanić, Kosara
Bjelobaba, Ivana
Maso Previde, Rafael
Stojilković, Stanko
Document Type:
Conference object (Published version)
,
© Bioscientifica 2023
Metadata
Show full item recordAbstract:
Simultaneous knockout of the neuroendocrine marker genes Ptprn and Ptprn2,
which encode the protein tyrosine phosphatase receptors N and N2, respectively,
causes infertility of female mice while males are fertile. To clarify the mechanism of
sex-specific roles of Ptprn and Ptprn2 in mice reproduction, we analyzed the effects
of their double knockout (DKO) on the hypothalamic-pituitary-gonadal axis. In
DKO females, a delay in puberty and lack of ovulation were observed, supplemented
by changes in ovarian gene expression and steroidogenesis. In DKO males, the
testicular gene expression, steroidogenesis, and development of reproductive organs
were not affected. However, in both sexes, pituitary luteinizing hormone (LH) beta
gene expression and LH levels were reduced, while the calcium-mobilizing and LH
secretory actions of gonadotropin-releasing hormone (GnRH) receptors were
preserved. The expression of hypothalamic Gnrh1 and Kiss1 genes were also
reduced in DKO females and males. The density of immunoreactive GnRH fibers
was decreased in the median eminence in DKO females and males. The density of
immunoreactive kisspeptin fibers was also decreased in the rostral periventricular
region of the third ventricle of females and in the arcuate nucleus of females and
males. Therefore, infertility in DKO females cannot be explained only by sex specific gonadotroph impairment. Instead, changes in hypothalamic gene
expression, specifically Kiss1 in the rostral periventricular region of the third
ventricle, might provide an alternative hypothesis due to its sexual dimorphism and
involvement in puberty onset and ovulation.
Keywords:
receptors N and N2; gonadotropin-releasing hormone; DKO female mice; Kiss1 genesFunding / projects:
- NICH grant number : Z01 HD000195-29
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
In:
- 25th European Congress of Endocrinology; 2023 May 13-16; Istanbul, Turkey. Bioscientifica; 2023. p. P152. (Endocrine Abstracts; Vol. 90).