Characterization of MC3 and the other melancortin receptors (MC) in the hypothalamo-pituitary-gonadal system of the mouse

Dowejko, M.M. 2014. Characterization of MC3 and the other melancortin receptors (MC) in the hypothalamo-pituitary-gonadal system of the mouse. PhD thesis University of Westminster Faculty of Science and Technology

TitleCharacterization of MC3 and the other melancortin receptors (MC) in the hypothalamo-pituitary-gonadal system of the mouse
TypePhD thesis
AuthorsDowejko, M.M.
Abstract

Melanocortin receptors (MC, MC1–MC5) are GPCRs, activated with different affinities by the melanocortin peptides (α-, β-, γ-MSH and ACTH). MC3 has well characterised roles in both the central regulation of energy metabolism and peripheral inflammatory responses. The functions and distribution of MC3 and the other MC in tissues of the reproductive system are unclear. Compared to wild type mice (WT), an apparent decrease in fertility of MC3 null mice (MC3-/-) has been observed and hence it was the aim of this series of studies to characterize MC3 and the other MC in tissues of the mouse hypothalamo-pituitary-gonadal (HPG) system.

The relative mRNA expressions of the MC have been identified at each level of the HPG axes in both male and female mice. It appeared that the MC mRNA expression may be regulated by the reproductive state of an animal and may change with age. Two different forms of POMC mRNA have been confirmed in the reproductive axes of both genders implicating local melanocortin production. Localization of MC3 protein was unsuccessful due to a lack of specificity of all the antibodies applied. Ablation of MC3 led to a decrease in the total pituitary hormone content in both male and female mice. The histology of testes of MC3-/- mice at different ages were abnormal compared to WT. In vitro incubation of hemi-sected testes of Balb/c or C57BL/6 mice in varying concentrations of selective MC3 agonist had modulatory, although non-significant, effects on testosterone production. However, MC3 activation during an inflammatory-like state in the testis, inhibited nitrite production but had no effects on the release of cytokines. The inhibitory action of MC3 agonist on nitrite release was also apparent in the K9 Leydig cell line, which expresses all five isoforms of MC.

MC3 may be both directly and/or indirectly implicated in the control of the mouse HPG system. The anti-inflammatory action of testicular MC3 activation could lead to possible clinical applications of MC3 agonists in the treatment of inflammatory situations associated with the loss of fertility.

Year2014
FileMonika_DOWEJKO_2014.pdf
Publication dates
Completed2014

Related outputs

The melanocortin system in the male reproductive axis
Dowejko, M.M., Smith, C.L., Getting, S.J., Le Tissier, P. and Murray, J.F. 2014. The melanocortin system in the male reproductive axis. Endocrine Abstracts. 34, p. P338. doi:10.1530/endoabs.34.P338

Melanocortin receptor expression in the hypothalamo-pituitary-gonadal system of WT and MC3 null mice
Dowejko, M.M., Smith, C.L., Getting, S.J., Le Tissier, P. and Murray, J.F. 2014. Melanocortin receptor expression in the hypothalamo-pituitary-gonadal system of WT and MC3 null mice. International Congress of Neuroendocrinology 2014. Sydney 17-20 August 2014

Melanocortin 3 receptors (MC3) exert anti-inflammatory effects in mouse testicular inflammation by reducing nitric oxide (NO) release from Leydig cells
Dowejko, M.M., Smith, C.L., Getting, S.J., Le Tissier, P. and Murray, J.F. 2014. Melanocortin 3 receptors (MC3) exert anti-inflammatory effects in mouse testicular inflammation by reducing nitric oxide (NO) release from Leydig cells. Society for Reproduction and Fertility Conference. EICC2, Edinburgh 1-2 September 2014

Melanocortin 3 receptor (MC3) activation effects on testicular testosterone and nitrite production in vitro
Dowejko, M.M., Smith, C.L., Getting, S.J., Le Tissier, P. and Murray, J.F. 2013. Melanocortin 3 receptor (MC3) activation effects on testicular testosterone and nitrite production in vitro. Society for Reproduction and Fertility (SRF) Annual Conference. Cambridge 11th July 2013

Expression of melanocortin 3 receptors (MC3) in the reproductive axes of both male and female mice
Dowejko, M.M., Smith, C.L., Getting, S.J., Le Tissier, P. and Murray, J.F. 2012. Expression of melanocortin 3 receptors (MC3) in the reproductive axes of both male and female mice. Society for Reproduction and Fertility. Edinburgh 9th - 11th July 2012

Total pituitary hormone content in wild type and MC3 null male and female mice
Dowejko, M.M., Smith, C.L., Getting, S.J., Perretti, M., Le Tissier, P. and Murray, J.F. 2011. Total pituitary hormone content in wild type and MC3 null male and female mice. British Society for Neuroendocrinology. Cambridge 3rd - 5th July 2011

Comparison between the total pituitary hormone content in wild type and melanocortin 3 receptor (MC3) null male and female mice
Dowejko, M.M., Smith, C.L., Getting, S.J., Perretti, M., Le Tissier, P. and Murray, J.F. 2011. Comparison between the total pituitary hormone content in wild type and melanocortin 3 receptor (MC3) null male and female mice. Society for Reproduction and Fertility. Brighton 11th - 13th July 2011

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