Cited by 112Hypothalamic control of reproductive hormonesReproductive Biology and FertilitySperm and Testicular Function

Functional Characterization of Genetically Labeled Gonadotropes

Wen, Shuping, Schwarz, Jürgen R., Niculescu, Dragos, Dinu, Crenguta, Bauer, Christiane K., Hirdes, Wiebke, Boehm, Ulrich·2008·Endocrinology

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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Crossref · 10.1210/en.2007-1502

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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
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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