Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats
Elizabeth D. Kirby, Anna C. Geraghty, Takayoshi Ubuka, George E. Bentley, Daniela Kaufer
The subjective experience of stress leads to reproductive dysfunction in many species, including rodents and humans. Stress effects on reproduction result from multilevel interactions between the hormonal stress response system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis, and the hormonal reproductive system, i.e., the hypothalamic-pituitary-gonadal (HPG) axis. A novel negative regulator of the HPG axis known as gonadotropin-inhibitory hormone (GnIH) was recently discovered in quail, and orthologous neuropeptides known as RFamide-related peptides (RFRPs) have also been identified in rodents and primates. It is currently unknown, however, whether GnIH/RFRPs influence HPG axis activity in response to stress. We show here that both acute and chronic immobilization stress lead to an up-regulation of RFRP expression in the dorsomedial hypothalamus (DMH) of adult male rats and that this increase in RFRP is associated with inhibition of downstream HPG activity.Wealso show that adrenalectomy blocks the stress-induced increase in RFRP expression. Immunohistochemistry revealed that 53% of RFRP cells express receptors for glucocorticoids (GCs), indicating that adrenal GCs can mediate the stress effect through direct action on RFRP cells. It is thought that stress effects on central control of reproduction are largely mediated by direct or indirect effects on GnRH-secreting neurons. Our data show that stress-induced increases in adrenal GCs cause an increase in RFRP that contributes to hypothalamic suppression of reproductive function. This novel insight into HPA-HPG interaction provides a paradigm shift for work on stress-related reproductive dysfunction and infertility, and indicates that future work on stress and reproductive system interactions must include investigation of the role of GnIH/RFRP.
Published - 2009 Jul 7
Luteinizing Hormone
RFamide peptide
Adrenalectomy
Glucocorticoid Receptors
Neuropeptides
GnIH
RFRP
Kirby, E. D., Geraghty, A. C., Ubuka, T., Bentley, G. E., & Kaufer, D. (2009). Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. Proceedings of the National Academy of Sciences of the United States of America, 106(27), 11324-11329. https://doi.org/10.1073/pnas.0901176106
Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. / Kirby, Elizabeth D.; Geraghty, Anna C.; Ubuka, Takayoshi; Bentley, George E.; Kaufer, Daniela.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 27, 07.07.2009, p. 11324-11329.
Kirby, ED, Geraghty, AC, Ubuka, T, Bentley, GE & Kaufer, D 2009, 'Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 27, pp. 11324-11329. https://doi.org/10.1073/pnas.0901176106
Kirby ED, Geraghty AC, Ubuka T, Bentley GE, Kaufer D. Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. Proceedings of the National Academy of Sciences of the United States of America. 2009 Jul 7;106(27):11324-11329. https://doi.org/10.1073/pnas.0901176106
Kirby, Elizabeth D. ; Geraghty, Anna C. ; Ubuka, Takayoshi ; Bentley, George E. ; Kaufer, Daniela. / Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 27. pp. 11324-11329.
@article{56f02c887a044719963388875faeb506,
title = "Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats",
abstract = "The subjective experience of stress leads to reproductive dysfunction in many species, including rodents and humans. Stress effects on reproduction result from multilevel interactions between the hormonal stress response system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis, and the hormonal reproductive system, i.e., the hypothalamic-pituitary-gonadal (HPG) axis. A novel negative regulator of the HPG axis known as gonadotropin-inhibitory hormone (GnIH) was recently discovered in quail, and orthologous neuropeptides known as RFamide-related peptides (RFRPs) have also been identified in rodents and primates. It is currently unknown, however, whether GnIH/RFRPs influence HPG axis activity in response to stress. We show here that both acute and chronic immobilization stress lead to an up-regulation of RFRP expression in the dorsomedial hypothalamus (DMH) of adult male rats and that this increase in RFRP is associated with inhibition of downstream HPG activity.Wealso show that adrenalectomy blocks the stress-induced increase in RFRP expression. Immunohistochemistry revealed that 53{\%} of RFRP cells express receptors for glucocorticoids (GCs), indicating that adrenal GCs can mediate the stress effect through direct action on RFRP cells. It is thought that stress effects on central control of reproduction are largely mediated by direct or indirect effects on GnRH-secreting neurons. Our data show that stress-induced increases in adrenal GCs cause an increase in RFRP that contributes to hypothalamic suppression of reproductive function. This novel insight into HPA-HPG interaction provides a paradigm shift for work on stress-related reproductive dysfunction and infertility, and indicates that future work on stress and reproductive system interactions must include investigation of the role of GnIH/RFRP.",
keywords = "GnIH, Reproduction, RFRP",
author = "Kirby, {Elizabeth D.} and Geraghty, {Anna C.} and Takayoshi Ubuka and Bentley, {George E.} and Daniela Kaufer",
doi = "10.1073/pnas.0901176106",
T1 - Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats
AU - Kirby, Elizabeth D.
AU - Geraghty, Anna C.
AU - Ubuka, Takayoshi
AU - Bentley, George E.
AU - Kaufer, Daniela
N2 - The subjective experience of stress leads to reproductive dysfunction in many species, including rodents and humans. Stress effects on reproduction result from multilevel interactions between the hormonal stress response system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis, and the hormonal reproductive system, i.e., the hypothalamic-pituitary-gonadal (HPG) axis. A novel negative regulator of the HPG axis known as gonadotropin-inhibitory hormone (GnIH) was recently discovered in quail, and orthologous neuropeptides known as RFamide-related peptides (RFRPs) have also been identified in rodents and primates. It is currently unknown, however, whether GnIH/RFRPs influence HPG axis activity in response to stress. We show here that both acute and chronic immobilization stress lead to an up-regulation of RFRP expression in the dorsomedial hypothalamus (DMH) of adult male rats and that this increase in RFRP is associated with inhibition of downstream HPG activity.Wealso show that adrenalectomy blocks the stress-induced increase in RFRP expression. Immunohistochemistry revealed that 53% of RFRP cells express receptors for glucocorticoids (GCs), indicating that adrenal GCs can mediate the stress effect through direct action on RFRP cells. It is thought that stress effects on central control of reproduction are largely mediated by direct or indirect effects on GnRH-secreting neurons. Our data show that stress-induced increases in adrenal GCs cause an increase in RFRP that contributes to hypothalamic suppression of reproductive function. This novel insight into HPA-HPG interaction provides a paradigm shift for work on stress-related reproductive dysfunction and infertility, and indicates that future work on stress and reproductive system interactions must include investigation of the role of GnIH/RFRP.
AB - The subjective experience of stress leads to reproductive dysfunction in many species, including rodents and humans. Stress effects on reproduction result from multilevel interactions between the hormonal stress response system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis, and the hormonal reproductive system, i.e., the hypothalamic-pituitary-gonadal (HPG) axis. A novel negative regulator of the HPG axis known as gonadotropin-inhibitory hormone (GnIH) was recently discovered in quail, and orthologous neuropeptides known as RFamide-related peptides (RFRPs) have also been identified in rodents and primates. It is currently unknown, however, whether GnIH/RFRPs influence HPG axis activity in response to stress. We show here that both acute and chronic immobilization stress lead to an up-regulation of RFRP expression in the dorsomedial hypothalamus (DMH) of adult male rats and that this increase in RFRP is associated with inhibition of downstream HPG activity.Wealso show that adrenalectomy blocks the stress-induced increase in RFRP expression. Immunohistochemistry revealed that 53% of RFRP cells express receptors for glucocorticoids (GCs), indicating that adrenal GCs can mediate the stress effect through direct action on RFRP cells. It is thought that stress effects on central control of reproduction are largely mediated by direct or indirect effects on GnRH-secreting neurons. Our data show that stress-induced increases in adrenal GCs cause an increase in RFRP that contributes to hypothalamic suppression of reproductive function. This novel insight into HPA-HPG interaction provides a paradigm shift for work on stress-related reproductive dysfunction and infertility, and indicates that future work on stress and reproductive system interactions must include investigation of the role of GnIH/RFRP.
KW - GnIH
KW - RFRP
U2 - 10.1073/pnas.0901176106
DO - 10.1073/pnas.0901176106