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Pituitary Gonadotrophic Hormone Synthesis, Secretion, Subunit Gene Expression and Cell Structure in Normal and Follicle-Stimulating Hormone β Knockout, Follicle-Stimulating Hormone Receptor Knockout, Luteinising Hormone Receptor Knockout, Hypogonadal and Ovariectomised Female Mice

Abel, M. H. ; Widen, A. LU orcid ; Wang, X. LU ; Huhtaniemi, I. LU ; Pakarinen, P. ; Kumar, T. R. and Christian, H. C. (2014) In Journal of Neuroendocrinology 26(11). p.785-795
Abstract

To investigate the relationship between gonadotroph function and ultrastructure, we have compared, in parallel in female mice, the effects of several different mutations that perturb the hypothalamic-pituitary-gonadal axis. Specifically, serum and pituitary gonadotrophin concentrations, gonadotrophin gene expression, gonadotroph structure and number were measured. Follicle-stimulating hormone β knockout (FSHβKO), follicle-stimulating hormone receptor knockout (FSHRKO), luteinising hormone receptor knockout (LuRKO), hypogonadal (hpg) and ovariectomised mice were compared with control wild-type or heterozygote female mice. Serum levels of LH were elevated in FSHβKO and FSHRKO compared to heterozygote females, reflecting the likely... (More)

To investigate the relationship between gonadotroph function and ultrastructure, we have compared, in parallel in female mice, the effects of several different mutations that perturb the hypothalamic-pituitary-gonadal axis. Specifically, serum and pituitary gonadotrophin concentrations, gonadotrophin gene expression, gonadotroph structure and number were measured. Follicle-stimulating hormone β knockout (FSHβKO), follicle-stimulating hormone receptor knockout (FSHRKO), luteinising hormone receptor knockout (LuRKO), hypogonadal (hpg) and ovariectomised mice were compared with control wild-type or heterozygote female mice. Serum levels of LH were elevated in FSHβKO and FSHRKO compared to heterozygote females, reflecting the likely decreased oestrogen production in KO females, as demonstrated by the threadlike uteri and acyclicity. As expected, there was no detectable FSH in the serum or pituitary and an absence of expression of the FSHβ subunit gene in FSHβKO mice. However, there was a significant increase in expression of the FSHβ and LHβ subunit genes in FSHRKO female mice. The morphology of FSHβKO and FSHRKO gonadotrophs was not significantly different from the control, except that secretory granules in FSHRKO gonadotrophs were larger in diameter. In LuRKO and ovariectomised mice, stimulation of LHβ and FSHβ mRNA, as well as serum protein concentrations, were reflected in subcellular changes in gonadotroph morphology, including more dilated rough endoplasmic reticula and fewer, larger secretory granules. In the gonadotophin-releasing hormone deficient hpg mouse, gonadotrophin mRNA and protein levels were significantly lower than in control mice and gonadotrophs were correspondingly smaller with less abundant endoplasmic reticula and reduced numbers of secretory granules. In summary, major differences in pituitary content and serum concentrations of the gonadotrophins LH and FSH were found between control and mutant female mice. These changes were associated with changes in expression of the gonadotrophin subunit genes and were reflected in the cellular structure and secretory granule appearance within the gonadotroph cells.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
anterior pituitary, follicle-stimulating hormone, gonadotrophs, luteinising hormone, ultrastructure
in
Journal of Neuroendocrinology
volume
26
issue
11
pages
785 - 795
publisher
Wiley-Blackwell
external identifiers
  • scopus:85007109955
ISSN
0953-8194
DOI
10.1111/jne.12178
language
English
LU publication?
no
additional info
Publisher Copyright: © 2014 British Society for Neuroendocrinology
id
b73fb956-ab52-4295-8f2e-e719046e133f
date added to LUP
2024-04-23 16:39:07
date last changed
2025-04-04 15:28:58
@article{b73fb956-ab52-4295-8f2e-e719046e133f,
  abstract     = {{<p>To investigate the relationship between gonadotroph function and ultrastructure, we have compared, in parallel in female mice, the effects of several different mutations that perturb the hypothalamic-pituitary-gonadal axis. Specifically, serum and pituitary gonadotrophin concentrations, gonadotrophin gene expression, gonadotroph structure and number were measured. Follicle-stimulating hormone β knockout (FSHβKO), follicle-stimulating hormone receptor knockout (FSHRKO), luteinising hormone receptor knockout (LuRKO), hypogonadal (hpg) and ovariectomised mice were compared with control wild-type or heterozygote female mice. Serum levels of LH were elevated in FSHβKO and FSHRKO compared to heterozygote females, reflecting the likely decreased oestrogen production in KO females, as demonstrated by the threadlike uteri and acyclicity. As expected, there was no detectable FSH in the serum or pituitary and an absence of expression of the FSHβ subunit gene in FSHβKO mice. However, there was a significant increase in expression of the FSHβ and LHβ subunit genes in FSHRKO female mice. The morphology of FSHβKO and FSHRKO gonadotrophs was not significantly different from the control, except that secretory granules in FSHRKO gonadotrophs were larger in diameter. In LuRKO and ovariectomised mice, stimulation of LHβ and FSHβ mRNA, as well as serum protein concentrations, were reflected in subcellular changes in gonadotroph morphology, including more dilated rough endoplasmic reticula and fewer, larger secretory granules. In the gonadotophin-releasing hormone deficient hpg mouse, gonadotrophin mRNA and protein levels were significantly lower than in control mice and gonadotrophs were correspondingly smaller with less abundant endoplasmic reticula and reduced numbers of secretory granules. In summary, major differences in pituitary content and serum concentrations of the gonadotrophins LH and FSH were found between control and mutant female mice. These changes were associated with changes in expression of the gonadotrophin subunit genes and were reflected in the cellular structure and secretory granule appearance within the gonadotroph cells.</p>}},
  author       = {{Abel, M. H. and Widen, A. and Wang, X. and Huhtaniemi, I. and Pakarinen, P. and Kumar, T. R. and Christian, H. C.}},
  issn         = {{0953-8194}},
  keywords     = {{anterior pituitary; follicle-stimulating hormone; gonadotrophs; luteinising hormone; ultrastructure}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{11}},
  pages        = {{785--795}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Neuroendocrinology}},
  title        = {{Pituitary Gonadotrophic Hormone Synthesis, Secretion, Subunit Gene Expression and Cell Structure in Normal and Follicle-Stimulating Hormone β Knockout, Follicle-Stimulating Hormone Receptor Knockout, Luteinising Hormone Receptor Knockout, Hypogonadal and Ovariectomised Female Mice}},
  url          = {{http://dx.doi.org/10.1111/jne.12178}},
  doi          = {{10.1111/jne.12178}},
  volume       = {{26}},
  year         = {{2014}},
}