Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis.
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Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis. / Wen, Shuping; Ai, Wei; Alim, Zahara; Boehm, Ulrich.
in: P NATL ACAD SCI USA, Jahrgang 107, Nr. 37, 37, 2010, S. 16372-16377.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Embryonic gonadotropin-releasing hormone signaling is necessary for maturation of the male reproductive axis.
AU - Wen, Shuping
AU - Ai, Wei
AU - Alim, Zahara
AU - Boehm, Ulrich
PY - 2010
Y1 - 2010
N2 - 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 GnRHR-expressing 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 hormone-expressing gonadotropes, but not follicle-stimulating hormone-expressing 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.
AB - 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 GnRHR-expressing 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 hormone-expressing gonadotropes, but not follicle-stimulating hormone-expressing 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.
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Gene Expression Regulation, Developmental
KW - Signal Transduction
KW - Mice, Transgenic
KW - Gonadotropin-Releasing Hormone metabolism
KW - Hypogonadism genetics
KW - Hypothalamus metabolism
KW - Pituitary Gland, Anterior embryology
KW - Receptors, LHRH genetics
KW - Sexual Maturation
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Mice
KW - Gene Expression Regulation, Developmental
KW - Signal Transduction
KW - Mice, Transgenic
KW - Gonadotropin-Releasing Hormone metabolism
KW - Hypogonadism genetics
KW - Hypothalamus metabolism
KW - Pituitary Gland, Anterior embryology
KW - Receptors, LHRH genetics
KW - Sexual Maturation
M3 - SCORING: Zeitschriftenaufsatz
VL - 107
SP - 16372
EP - 16377
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 37
M1 - 37
ER -
