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Attenuated hypothalamic responses to α-melanocyte stimulating hormone during pregnancy in the rat.
J Physiol. 2016 Feb 15; 594(4):1087-101.JP

Abstract

KEY POINTS

Increased appetite and weight gain occurs during pregnancy, associated with development of leptin resistance, and satiety responses to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) are suppressed. This study investigated hypothalamic responses to α-MSH during pregnancy, using c-fos expression in specific hypothalamic nuclei as a marker of neuronal signalling, and in vivo electrophysiology in supraoptic nucleus (SON) oxytocin neurons, as a representative α-MSH-responsive neuronal population that shows a well-characterised α-MSH-induced inhibition of firing. While icv injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, supraoptic, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, this response was suppressed in pregnant rats. Similarly, SON oxytocin neurons in pregnant rats did not demonstrate characteristic α-MSH-induced inhibition of firing that was observed in non-pregnant animals. Given the known functions of α-MSH in the hypothalamus, the attenuated responses are likely to facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy.

ABSTRACT

During pregnancy, a state of positive energy balance develops to support the growing fetus and to deposit fat in preparation for the subsequent metabolic demands of lactation. As part of this maternal adaptation, the satiety response to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) is suppressed. To investigate whether pregnancy is associated with changes in the response of hypothalamic α-MSH target neurons, non-pregnant and pregnant rats were treated with α-MSH or vehicle and c-fos expression in hypothalamic nuclei was then examined. Furthermore, the firing rate of supraoptic nucleus (SON) oxytocin neurons, a known α-MSH responsive neuronal population, was examined in non-pregnant and pregnant rats following α-MSH treatment. Intracerebroventricular injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, but no significant increase was observed in any of these regions in pregnant rats. In the SON, α-MSH did induce expression of c-fos during pregnancy, but this was significantly reduced compared to that observed in the non-pregnant group. Furthermore, during pregnancy, SON oxytocin neurons did not demonstrate the characteristic α-MSH-induced inhibition of firing rate that was observed in non-pregnant animals. Melanocortin receptor mRNA levels during pregnancy were similar to non-pregnant animals, suggesting that receptor down-regulation is unlikely to be a mechanism underlying the attenuated responses to α-MSH during pregnancy. Given the known functions of α-MSH in the hypothalamus, the attenuated responses will facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy.

Authors+Show Affiliations

Department of Anatomy and Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.Department of Physiology and Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.Department of Anatomy and Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.Department of Anatomy and Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.Department of Physiology and Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.Department of Anatomy and Centre for Neuroendocrinology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26613967

Citation

Ladyman, S R., et al. "Attenuated Hypothalamic Responses to Α-melanocyte Stimulating Hormone During Pregnancy in the Rat." The Journal of Physiology, vol. 594, no. 4, 2016, pp. 1087-101.
Ladyman SR, Augustine RA, Scherf E, et al. Attenuated hypothalamic responses to α-melanocyte stimulating hormone during pregnancy in the rat. J Physiol. 2016;594(4):1087-101.
Ladyman, S. R., Augustine, R. A., Scherf, E., Phillipps, H. R., Brown, C. H., & Grattan, D. R. (2016). Attenuated hypothalamic responses to α-melanocyte stimulating hormone during pregnancy in the rat. The Journal of Physiology, 594(4), 1087-101. https://doi.org/10.1113/JP271605
Ladyman SR, et al. Attenuated Hypothalamic Responses to Α-melanocyte Stimulating Hormone During Pregnancy in the Rat. J Physiol. 2016 Feb 15;594(4):1087-101. PubMed PMID: 26613967.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuated hypothalamic responses to α-melanocyte stimulating hormone during pregnancy in the rat. AU - Ladyman,S R, AU - Augustine,R A, AU - Scherf,E, AU - Phillipps,H R, AU - Brown,C H, AU - Grattan,D R, PY - 2015/09/17/received PY - 2015/11/23/accepted PY - 2015/11/29/entrez PY - 2015/11/29/pubmed PY - 2016/11/5/medline SP - 1087 EP - 101 JF - The Journal of physiology JO - J Physiol VL - 594 IS - 4 N2 - KEY POINTS: Increased appetite and weight gain occurs during pregnancy, associated with development of leptin resistance, and satiety responses to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) are suppressed. This study investigated hypothalamic responses to α-MSH during pregnancy, using c-fos expression in specific hypothalamic nuclei as a marker of neuronal signalling, and in vivo electrophysiology in supraoptic nucleus (SON) oxytocin neurons, as a representative α-MSH-responsive neuronal population that shows a well-characterised α-MSH-induced inhibition of firing. While icv injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, supraoptic, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, this response was suppressed in pregnant rats. Similarly, SON oxytocin neurons in pregnant rats did not demonstrate characteristic α-MSH-induced inhibition of firing that was observed in non-pregnant animals. Given the known functions of α-MSH in the hypothalamus, the attenuated responses are likely to facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy. ABSTRACT: During pregnancy, a state of positive energy balance develops to support the growing fetus and to deposit fat in preparation for the subsequent metabolic demands of lactation. As part of this maternal adaptation, the satiety response to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) is suppressed. To investigate whether pregnancy is associated with changes in the response of hypothalamic α-MSH target neurons, non-pregnant and pregnant rats were treated with α-MSH or vehicle and c-fos expression in hypothalamic nuclei was then examined. Furthermore, the firing rate of supraoptic nucleus (SON) oxytocin neurons, a known α-MSH responsive neuronal population, was examined in non-pregnant and pregnant rats following α-MSH treatment. Intracerebroventricular injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, but no significant increase was observed in any of these regions in pregnant rats. In the SON, α-MSH did induce expression of c-fos during pregnancy, but this was significantly reduced compared to that observed in the non-pregnant group. Furthermore, during pregnancy, SON oxytocin neurons did not demonstrate the characteristic α-MSH-induced inhibition of firing rate that was observed in non-pregnant animals. Melanocortin receptor mRNA levels during pregnancy were similar to non-pregnant animals, suggesting that receptor down-regulation is unlikely to be a mechanism underlying the attenuated responses to α-MSH during pregnancy. Given the known functions of α-MSH in the hypothalamus, the attenuated responses will facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy. SN - 1469-7793 UR - https://www.unboundmedicine.com/medline/citation/26613967/Attenuated_hypothalamic_responses_to_α_melanocyte_stimulating_hormone_during_pregnancy_in_the_rat_ L2 - https://doi.org/10.1113/JP271605 DB - PRIME DP - Unbound Medicine ER -