Vasoactive Intestinal Peptide Modulation of the Steroid-induced LH Surge Involves Kisspeptin Signaling in Young but Not in Middle-aged Female Rats

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2014 Mar 25

PMID 24654782

Citations 10

Authors

Alexander S Kauffman

Yan Sun

Joshua Kim

Azim R Khan

Jun Shu

Genevieve Neal-Perry

Affiliations

Soon will be listed here.

Abstract

Age-related LH surge dysfunction in middle-aged rats is characterized, in part, by reduced responsiveness to estradiol (E2)-positive feedback and reduced hypothalamic kisspeptin neurotransmission. Vasoactive intestinal peptide (VIP) neurons in the suprachiasmatic nucleus project to hypothalamic regions that house kisspeptin neurons. Additionally, middle-age females express less VIP mRNA in the suprachiasmatic nucleus on the day of the LH surge and intracerebroventricular (icv) VIP infusion restores LH surges. We tested the hypothesis that icv infusion of VIP modulates the LH surge through effects on the kisspeptin and RFamide-related peptide-3 (RFRP-3; an estradiol-regulated inhibitor of GnRH neurons) neurotransmitter systems. Brains were collected for in situ hybridization analyses from ovariectomized and ovarian hormone-primed young and middle-aged females infused with VIP or saline. The percentage of GnRH and Kiss1 cells coexpressing cfos and total Kiss1 mRNA were reduced in saline-infused middle-aged compared with young females. In young females, VIP reduced the percentage of GnRH and Kiss1 cells coexpressing cfos, suggesting that increased VIP signaling in young females adversely affected the function of Kiss1 and GnRH neurons. In middle-aged females, VIP increased the percentage of GnRH but not Kiss1 neurons coexpressing cfos, suggesting VIP affects LH release in middle-aged females through kisspeptin-independent effects on GnRH neurons. Neither reproductive age nor VIP affected Rfrp cell number, Rfrp mRNA levels per cell, or coexpression of cfos in Rfrp cells. These data suggest that VIP differentially affects activation of GnRH and kisspeptin neurons of female rats in an age-dependent manner.

Citing Articles

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Corticosterone Blocks Ovarian Cyclicity and the LH Surge via Decreased Kisspeptin Neuron Activation in Female Mice.

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References

Khan A, Kauffman A . The role of kisspeptin and RFamide-related peptide-3 neurones in the circadian-timed preovulatory luteinising hormone surge. J Neuroendocrinol. 2011; 24(1):131-43. PMC: 3384704. DOI: 10.1111/j.1365-2826.2011.02162.x. View

van der Beek E, Wiegant V, van der Donk H, Van Den Hurk R, Buijs R . Lesions of the suprachiasmatic nucleus indicate the presence of a direct vasoactive intestinal polypeptide-containing projection to gonadotrophin-releasing hormone neurons in the female rat. J Neuroendocrinol. 1993; 5(2):137-44. DOI: 10.1111/j.1365-2826.1993.tb00373.x. View

Rizwan M, Poling M, Corr M, Cornes P, Augustine R, Quennell J . RFamide-related peptide-3 receptor gene expression in GnRH and kisspeptin neurons and GnRH-dependent mechanism of action. Endocrinology. 2012; 153(8):3770-9. DOI: 10.1210/en.2012-1133. View

Finn P, Steiner R, Clifton D . Temporal patterns of gonadotropin-releasing hormone (GnRH), c-fos, and galanin gene expression in GnRH neurons relative to the luteinizing hormone surge in the rat. J Neurosci. 1998; 18(2):713-9. PMC: 6792541. View

Le W, Wise P, Murphy A, Coolen L, Hoffman G . Parallel declines in Fos activation of the medial anteroventral periventricular nucleus and LHRH neurons in middle-aged rats. Endocrinology. 2001; 142(11):4976-82. DOI: 10.1210/endo.142.11.8470. View

Semaan S, Murray E, Poling M, Dhamija S, Forger N, Kauffman A . BAX-dependent and BAX-independent regulation of Kiss1 neuron development in mice. Endocrinology. 2010; 151(12):5807-17. PMC: 2999490. DOI: 10.1210/en.2010-0783. View

Ducret E, Anderson G, Herbison A . RFamide-related peptide-3, a mammalian gonadotropin-inhibitory hormone ortholog, regulates gonadotropin-releasing hormone neuron firing in the mouse. Endocrinology. 2009; 150(6):2799-804. DOI: 10.1210/en.2008-1623. View

Cooper R, Conn P, Walker R . Characterization of the LH surge in middle-aged female rats. Biol Reprod. 1980; 23(3):611-5. DOI: 10.1095/biolreprod23.3.611. View

Weiland N, Cohen I, Wise P . Age-associated alterations in catecholaminergic concentrations, neuronal activity, and alpha 1 receptor densities in female rats. Neurobiol Aging. 1989; 10(4):323-9. DOI: 10.1016/0197-4580(89)90043-2. View

10.

Ishii M, Matsumoto K, Matsui H, Seki N, Matsumoto H, Ishikawa K . Reduced responsiveness of kisspeptin neurons to estrogenic positive feedback associated with age-related disappearance of LH surge in middle-age female rats. Gen Comp Endocrinol. 2013; 193:121-9. DOI: 10.1016/j.ygcen.2013.06.024. View

11.

Liu X, Lee K, Herbison A . Kisspeptin excites gonadotropin-releasing hormone neurons through a phospholipase C/calcium-dependent pathway regulating multiple ion channels. Endocrinology. 2008; 149(9):4605-14. PMC: 6116891. DOI: 10.1210/en.2008-0321. View

12.

van der Beek E, van Oudheusden H, Buijs R, van der Donk H, Van Den Hurk R, Wiegant V . Preferential induction of c-fos immunoreactivity in vasoactive intestinal polypeptide-innervated gonadotropin-releasing hormone neurons during a steroid-induced luteinizing hormone surge in the female rat. Endocrinology. 1994; 134(6):2636-44. DOI: 10.1210/endo.134.6.8194489. View

13.

Gibson E, Humber S, Jain S, Williams 3rd W, Zhao S, Bentley G . Alterations in RFamide-related peptide expression are coordinated with the preovulatory luteinizing hormone surge. Endocrinology. 2008; 149(10):4958-69. PMC: 2582915. DOI: 10.1210/en.2008-0316. View

14.

de la Iglesia H, Schwartz W . Minireview: timely ovulation: circadian regulation of the female hypothalamo-pituitary-gonadal axis. Endocrinology. 2005; 147(3):1148-53. DOI: 10.1210/en.2005-1311. View

15.

Smith J . Sex steroid regulation of kisspeptin circuits. Adv Exp Med Biol. 2013; 784:275-95. DOI: 10.1007/978-1-4614-6199-9_13. View

16.

Ottem E, Godwin J, Krishnan S, Petersen S . Dual-phenotype GABA/glutamate neurons in adult preoptic area: sexual dimorphism and function. J Neurosci. 2004; 24(37):8097-105. PMC: 6729791. DOI: 10.1523/JNEUROSCI.2267-04.2004. View

17.

Gerhold L, Wise P . Vasoactive intestinal polypeptide regulates dynamic changes in astrocyte morphometry: impact on gonadotropin-releasing hormone neurons. Endocrinology. 2006; 147(5):2197-202. DOI: 10.1210/en.2005-1262. View

18.

Clarkson J, dAnglemont de Tassigny X, Moreno A, Colledge W, Herbison A . Kisspeptin-GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. J Neurosci. 2008; 28(35):8691-7. PMC: 6670827. DOI: 10.1523/JNEUROSCI.1775-08.2008. View

19.

Cai A, Lehman M, Lloyd J, Wise P . Transplantation of fetal suprachiasmatic nuclei into middle-aged rats restores diurnal Fos expression in host. Am J Physiol. 1997; 272(1 Pt 2):R422-8. DOI: 10.1152/ajpregu.1997.272.1.R422. View

20.

Todd B, Merhi Z, Shu J, Etgen A, Neal-Perry G . Hypothalamic insulin-like growth factor-I receptors are necessary for hormone-dependent luteinizing hormone surges: implications for female reproductive aging. Endocrinology. 2010; 151(3):1356-66. PMC: 2840696. DOI: 10.1210/en.2009-1009. View