Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling.
Glucagon-like peptide-1 (GLP-1), a potent regulator of glucose homeostasis, is also produced in the central nervous system, where GLP-1 has been implicated in the neuroendocrine control of hypothalamic-pituitary function, food intake, and the response to stress. The finding that intracerebroventricular GLP-1 stimulates LH, TSH, corticosterone, and vasopressin secretion in rats prompted us to assess the neuroendocrine consequences of disrupting GLP-1 signaling in mice in vivo. Male GLP-1 receptor knockout (GLP-1R-/-) mice exhibit reduced gonadal weights, and females exhibit a slight delay in the onset of puberty; however, male and female GLP-1R-/- animals reproduce successfully and respond appropriately to fluid restriction. Although adrenal weights are reduced in GLP-1R-/- mice, hypothalamic CRH gene expression and circulating levels of corticosterone, thyroid hormone, testosterone, estradiol, and progesterone are normal in the absence of GLP-1R-/- signaling. Intriguingly, GLP-1R-/- mice exhibit paradoxically increased corticosterone responses to stress as well as abnormal responses to acoustic startle that are corrected by glucocorticoid treatment. These findings suggest that although GLP-1R signaling is not essential for development and basal function of the murine hypothalamic-pituitary-adrenal axis, abrogation of GLP-1 signaling is associated with impairment of the behavioral and neuroendocrine responses to stress.
MacLusky
N J
NJ
Department of Reproductive Science, University of Toronto, Ontario, Canada.
Cook
S
S
Scrocchi
L
L
Shin
J
J
Kim
J
J
Vaccarino
F
F
Asa
S L
SL
Drucker
D J
DJ
D000161:Acoustic Stimulation; D000311:Adrenal Glands / Q000254:growth & development; D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004958:Estradiol / Q000097:blood; D004971:Estrus; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000254:growth & development; D010902:Pituitary Gland / Q000254:growth & development; D011374:Progesterone / Q000097:blood; D051381:Rats; D018027:Receptors, Glucagon / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology*; D012741:Sexual Maturation / Q000502:physiology*; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology*; D013737:Testis / Q000254:growth & development; D013739:Testosterone / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood
C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D013963:Thyroid Hormones; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone