The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
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 the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
A new generation of Ca2+ indicators with greatly improved fluorescence properties.
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Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121
Visualizing an Olfactory Sensory Map
Mombaerts, P., Wang, F., Dulac, C. G., Chao, S. K., Nemes, A., Mendelsohn, M. M., Edmondson, J., & Axel, R. (1996) · Cell · doi:10.1016/s0092-8674(00)81387-2 · Cited by 1,992
Muscarinic activation of ionic currents measured by a new whole-cell recording method.
Horn, R., & Marty, A. (1988) · The Journal of general physiology · doi:10.1085/jgp.92.2.145 · Cited by 1,338
Knobil and Neill's Physiology of Reproduction
(2015) · Elsevier eBooks · doi:10.1016/c2011-1-07288-0 · Cited by 1,277
High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP
Rodríguez, C. I., Buchholz, F., Galloway, J. L., Sequerra, R., Kasper, J. S., Ayala, R., Stewart, A. F., & Dymecki, S. M. (2000) · Nature Genetics · doi:10.1038/75973 · Cited by 1,162
A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration
Buch, T., Heppner, F. L., Tertilt, C., Heinen, T. J. A. J., Kremer, M., Wunderlich, F. T., Jung, S., & Waisman, A. (2005) · Nature Methods · doi:10.1038/nmeth762 · Cited by 922
Gonadotropin-Releasing Hormone Receptors
Millar, R. P., Lu, Z.-L., Pawson, A. J., Flanagan, C. A., Morgan, K., & Maudsley, S. R. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0002 · Cited by 791
Ca2+-activated K+ channels: molecular determinants and function of the SK family
Stocker, M. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1516 · Cited by 534
Cited by
Sorted by citations
Gonadotropin regulation by pulsatile GnRH: Signaling and gene expression
Stamatiades, G. A., & Kaiser, U. B. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.10.015 · Cited by 293
GnRH signaling, the gonadotrope and endocrine control of fertility
Bliss, S. P., Navratil, A. M., Xie, J., & Roberson, M. S. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.04.002 · Cited by 259
Ion channels and signaling in the pituitary gland
Stojilkovic, S. S., Tabak, J., & Bertram, R. (2010) · Endocrine Reviews · doi:10.1210/er.2010-0005 · Cited by 229
GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression
Thompson, I. R., & Kaiser, U. B. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.09.012 · Cited by 199
Hormones in synergy: Regulation of the pituitary gonadotropin genes
Thackray, V. G., Mellon, P. L., & Coss, D. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.09.003 · Cited by 167
Metadata
- 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 › Reproductive Medicine › 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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