Extracellular Signal-Regulated Kinase 1 and 2 Are Not Required for GnRH Neuron Development and Normal Female Reproductive Axis Function in Mice
Abstract
Background/Aims: Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. Methods: GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1–/Erk2 fl/fl) to selectively delete ERK2 in GnRH neurons. Results: Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRH Cre+Erk1–/Erk2– mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. Conclusions: Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron.
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ERK double knockout conditionally in GnRH neurons did not impact fertility.
“Similar studies of ERK double knockout conditionally in GnRH neurons did not impact fertility14”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [14]
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- Authors
- Wierman, M. E., Xu, M., Pierce, A., Bliesner, B., Bliss, S. P., & Roberson, M. S.
- Affiliations
- Veterans Health Administration (US)
- Cornell University (US)
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2011-12-09
- Volume
- 95
- Issue
- 4
- Pages
- 289-296
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W1990059979
- Cited by
- 6
- References
- 21
- Citations by year
- 2020: 2 · 2019: 1 · 2016: 1 · 2014: 1 · 2012: 1
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD031191, R01HD31191, R01 HD34722, R01HD034722)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- ERK1, ERK2, GnRH neurons, gonadotropin-releasing hormone, ERK signaling, compensatory signaling pathways, female sexual maturation, estrous cyclicity
- MeSH terms
- Animals, Cell Count, Female, Gonadotropin-Releasing Hormone, Mice, Transgenic, Models, Biological, Neurons, Ovary, Reproduction, Gene Deletion, Integrases, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mice, Gonadotrophs, Neurogenesis
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