Targeted ablation of gonadotrophs in transgenic mice depresses prolactin but not growth hormone gene expression at birth as measured by quantitative mRNA detection

Vankelecom, Hugo; Seuntjens, Eve; Hauspie, Annelies; Denef, Carl

doi:10.1007/bf02256333

Cited by 11 publications

(9 citation statements)

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“…S8), suggesting a stereotyped cellular composition independent of GnRHR+ cell gonadotrope ablation. No ablation efficiency differences between FSH+ and LH+ gonadotropes were reported in transgenic mice using a α-GSU promoter fragment to express DTA (23)(24)(25). This might reflect earlier ablation, as α-GSU, which is a common α-glycoprotein subunit shared by LH, FSH, and TSH (26), is the first pituitary hormone transcript expressed during development at E10.5 (27).…”

Section: Discussionmentioning

confidence: 99%

Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis

Wen

Alim

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

100

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Gonadotropin-releasing hormone (GnRH) signaling regulates reproductive physiology in mammals. GnRH is released by a subset of hypothalamic neurons and binds to GnRH receptor (GnRHR) on gonadotropes in the anterior pituitary gland to control production and secretion of gonadotropins that in turn regulate the activity of the gonads. Central control of reproduction is well understood in adult animals, but GnRH signaling has also been implicated in the development of the reproductive axis. To investigate the role of GnRH signaling during development, we selectively ablated GnRHRexpressing cells in mice. This genetic strategy permitted us to identify an essential stage in male reproductive axis development, which depends on embryonic GnRH signaling. Our experiments revealed a striking dichotomy in the gonadotrope population of the fetal anterior pituitary gland. We show that luteinizing hormoneexpressing gonadotropes, but not follicle-stimulating hormoneexpressing gonadotropes, express the GnRHR at embryonic day 16.75. Furthermore, we demonstrate that an embryonic increase in luteinizing hormone secretion is needed to promote development of follicle-stimulating hormone-expressing gonadotropes, which might be mediated by paracrine interactions within the pituitary. Moreover, migration of GnRH neurons into the hypothalamus appeared normal with appropriate axonal connections to the median eminence, providing genetic evidence against autocrine regulation of GnRH neurons. Surprisingly, genetic ablation of GnRHR expressing cells significantly increased the number of GnRH neurons in the anterior hypothalamus, suggesting an unexpected role of GnRH signaling in establishing the size of the GnRH neuronal population. Our experiments define a functional role of embryonic GnRH signaling.gonadotropin-releasing hormone neurons | gonadotropin-releasing hormone receptor | gonadotrope development | diphtheria toxin | Cre recombinase R eproductive physiology in mammals is centrally regulated through the hypothalamic-pituitary-gonadal axis and depends on gonadotropin-releasing hormone (GnRH). GnRH signaling is well understood in adult animals, but has also been implicated in the development of the reproductive axis. The hormone is produced by a subset of neurons with a scattered distribution throughout the basal forebrain and released into the hypophyseal portal vasculature from axon terminals at the median eminence (1, 2). GnRH binds to the GnRH receptor (GnRHR), which is specifically expressed on gonadotrope cells in the anterior pituitary gland (3). GnRH signaling controls biosynthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) that in turn regulate development and activity of the ovaries and testes (4).Studies in mice suggest that the hypothalamic-pituitarygonadal axis might already be functional during embryonic development. GnRH neurons have migrated from their place of origin in the nasal placodes to their final destination in the forebrain (5) and project neurosecretory axons to the median emi...

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Section: Discussionmentioning

confidence: 99%

Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis

Wen

Alim

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

100

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“…The identities of the amplified fragments were confirmed by sequence analysis (performed by Lark Technologies, Essex, UK). PCR protocols for hormones have been optimized and validated previously in the laboratory (47). In general, PCR cycling consisted of the following temperature steps: 7 min at 95 C, followed by 35-50 cycles of denaturation, annealing, and extension, the details of which depend on the specific cDNA to be amplified (described in Table 1).…”

Section: Gene Expression Analysis By Rt-pcrmentioning

confidence: 99%

“…To inspect the reliability of the semiquantitative method, quantitative real-time RT-PCR was performed for a selection of the markers using the primers shown in Table 1 or other primers already published (47). As an additional control, another internal (normalization) standard (18S rRNA instead of L19 mRNA) was used.…”

Section: Gene Expression Analysis By Rt-pcrmentioning

confidence: 99%

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The Adult Pituitary Contains a Cell Population Displaying Stem/Progenitor Cell and Early Embryonic Characteristics

et al. 2005

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A side population (SP) has been identified in a number of tissues, where it typically represents a small population enriched in stem/progenitor cells. In this study we show that the adult mouse anterior pituitary (AP) also contains a characteristic SP displaying verapamil-sensitive Hoechst dye efflux capacity. A majority of the SP cells express stem cell antigen 1 at a high level (Sca1high). Using (semi)quantitative RT-PCR and immunofluorescence, we characterized the Sca1high SP as a population enriched in cells expressing stem/progenitor cell-associated factors and components of the Notch, Wnt, and sonic hedgehog signaling pathways, functional in stem cell homeostasis as well as in early pituitary embryogenesis. Lhx4, a transcription factor pivotal for early embryonic development of the AP, was only detected in the Sca1high SP, whereas Lhx3, in contrast to Lhx4 not down-regulated after AP development, was only found in the main population. The Sca1high SP was depleted from cells expressing phenotypic markers of differentiated AP cells (hormones), but contained a small proportion of folliculo-stellate cells. Stem cells of many tissues can clonally expand to nonadherent spheres in culture. Clonal spheres also developed in AP cell cultures. Spheres showed an expression pattern resembling that of Sca1high SP cells. Moreover, the sphere-initiating cells of the pituitary segregated to the SP and not to the main population. In conclusion, we show that the adult pituitary contains a hitherto undescribed population of cells with SP phenotype and clonal expansion capacity. These cells express (signaling) molecules generally found in stem/progenitor cells and/or operative during pituitary early embryonic development. These characteristics are supportive of a stem/progenitor cell phenotype.

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“…This paracrine stimulatory action was previously demonstrated in vivo by transgenic ablation of gonadotrophs in mice [30]. Vankelecom et al [37] demonstrate that this developmental influence is exerted at the transcriptional level by selective upregulation of prolactin gene expression.…”

Section: Targeted Ablation Of Gonadotrophs Depresses Prolactin Gene Ementioning

confidence: 83%

Biomedical Vignette

2003

J Biomed Sci

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Targeted ablation of gonadotrophs in transgenic mice depresses prolactin but not growth hormone gene expression at birth as measured by quantitative mRNA detection

Cited by 11 publications

References 36 publications

Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis

Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis

The Adult Pituitary Contains a Cell Population Displaying Stem/Progenitor Cell and Early Embryonic Characteristics

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