Functional Characterization of Genetically Labeled Gonadotropes
Abstract
Gonadotropes are crucial in the control of reproduction but difficult to isolate for functional analysis due to their scattered distribution in the anterior pituitary gland. We devised a binary genetic approach, and describe a new mouse model that allows visualization and manipulation of gonadotrope cells. Using gene targeting in embryonic stem cells, we generated mice in which Cre recombinase is coexpressed with the GnRH receptor, which is expressed in gonadotrope cells. We show that we can direct Cre-mediated recombination of a yellow fluorescent protein reporter allele specifically in gonadotropes within the anterior pituitary of these knock-in mice. More than 99% of gonadotropin-containing cells were labeled by yellow fluorescent protein fluorescence and readily identifiable in dissociated pituitary cell culture, allowing potentially unbiased sampling from the gonadotrope population. Using electrophysiology, calcium imaging, and the study of secretion on the single-cell level, the functional properties of gonadotropes isolated from male mice were analyzed. Our studies demonstrate a significant heterogeneity in the resting properties of gonadotropes and their responses to GnRH. About 50% of gonadotropes do not exhibit secretion of LH or FSH. Application of GnRH induced a broad range of both electrophysiological responses and increases in the intracellular calcium concentration. Our mouse model will also be able to direct expression of other Cre recombination-dependent reporter genes to gonadotropes and, therefore, represents a versatile new tool in the understanding of gonadotrope biology.
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In past studies, a pituitary-specific conditional ERK double knockout (ERKdko) was reported using ERK1 null and ERK2 floxed alleles combined with αGSU-Cre and GRIC drivers.
“In past studies, we reported a pituitary-specific conditional ERK double knockout (ERKdko) using the ERK1 null and ERK2 floxed alleles combined with a Cre recombinase driver regulated by the gene promoter for the α subunit to the glycoprotein hormones (αGSU)3,4 and the gonadotrope-specific Cre driver (GRIC)12,13.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [13]
This is the first report of a novel model of placental ERK gene deletion associated with expression of a GnRHR-Cre driver.
“this is the first report of a novel model of placental ERK gene deletion associated with expression of a GnRHR-Cre driver3,12,13”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [13]
Loss of ERK signaling within the gonadotrope is detrimental to the function of the hypothalamic-pituitary-gonadal axis and the placenta.
“While loss of ERK signaling within the gonadotrope has been shown to be detrimental to the function of the hypothalamic-pituitary-gonadal axis as well as the placenta”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [13]
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Ovulation is triggered by a cyclical modulation of gonadotropes into a hyperexcitable state
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Myostatin is a major endocrine driver of follicle-stimulating hormone synthesisPreprint
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Cell Networks in Endocrine/Neuroendocrine Gland Function
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- Authors
- Wen, S., Schwarz, J. R., Niculescu, D., Dinu, C., Bauer, C. K., Hirdes, W., & Boehm, U.
- Affiliations
- Universität Hamburg (DE)
- Institute for Neural Signal Transduction (S.W., J.R.S., D.N., C.D., W.H., U.B.), Center for Molecular Neurobiology, D-20253 Hamburg, Germany
- University Medical Center Hamburg-Eppendorf (DE)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-03-06
- Volume
- 149
- Issue
- 6
- Pages
- 2701-2711
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2070693587
- Cited by
- 112
- References
- 38
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 5
- FWCI
- 8.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- gonadotrophs, GnRH receptor, Cre recombinase, anterior pituitary, GnRH response, luteinizing hormone secretion, follicle-stimulating hormone secretion, intracellular calcium, single-cell secretion
- MeSH terms
- Animals, Calcium, Electrophysiology, Exons, Gonadotropins, Humans, Mice, Transgenic, Pituitary Gland, Anterior, Potassium, Receptors, LHRH, Patch-Clamp Techniques, Mice, Gonadotrophs
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