File:Male genital molecular signaling 01.jpg

Male Sex Development

Normal male phenotypic sex development highlighting the role of DHH. Testis determination requires SRY and one DAX1 copy, whilst with two DAX1 copies and a lack of SRY an ovary is determined. In the bipotential gonad, SF1, WT1 and GATA4 upregulate SRY which in turn upregulates SOX9; SOX9 is pivotal to testis determination. Upregulation of SRY and SOX9 overcomes the action of genes promoting female sex development including DAX1 and β-catenin. With upregulation of SOX9, multiple feed-forward loops then accelerate male pathway commitment. Other genes, including DHH, as well as growth factors also have roles in promoting testis determination. Following testis determination, Sertoli cells secrete AMH leading to Müllerian duct regres- sion; Müllerian ducts would otherwise form the fallopian tubes, uterus, cervix and upper vagina. Sertoli cells also secrete DHH which is important for Leydig cell development and Sertoli-peritubular cell interaction. Responding to luteinizing hormone (via LHCGR), a functional Leydig cell produces testosterone via steroidogenesis, requiring SF1 and steroidogenesis enzymes. Converted to DHT via 5α-reductase, testosterone and DHT induce Wolffian duct differentiation (leading to vas deferens, seminal vesicle and prostate formation) and external genitalia masculinization through actions on the androgen receptor. In the absence of functional Leydig cells female external genitalia form and testes fail to descend. Blue block arrows indicate DHH’s involvement in male sex de- velopment. Lines ending in an arrow denote a positive/up-regulating effect whilst lines ending in a perpendicular bar indicate a negative/down-regulating effect.

Abbreviations: AMH– Anti-Müllerian hormone, ATRX– X-linked alpha thalassemia and mental retardation, DAX1– dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1, DHH– desert hedgehog, DHT– dihydrotestosterone, FGF9– fibroblast growth factor 9, INSL3– insulin-like protein 3, LHCGR– Luteinizing hormone common G-protein receptor, NGFs– nerve growth factors, PDGFs– platelet derived growth factors, PGD2– prosta- glandin D2, RSPO1– R-spondin-1, SF1– steroidogenic factor-1, SRY– sex determining region on the Y chromosome, WT1– Wilms’ tumour suppressor gene 1

Reference

Rothacker KM, Ayers KL, Tang D, Joshi K, van den Bergen JA, Robevska G, Samnakay N, Nagarajan L, Francis K, Sinclair AH & Choong CS. (2018). A novel, homozygous mutation indesert hedgehog(DHH) in a 46, XY patient with dysgenetic testes presenting with primary amenorrhoea: a case report. Int J Pediatr Endocrinol , 2018, 2. PMID: 29507583 DOI.

Copyright

© Rothacker KM, Ayers KL, Tang D, Joshi K, van den Bergen JA, Robevska G, Samnakay N, Nagarajan L, Francis K, Sinclair AH, Choong CS. 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Cite this page: Hill, M.A. (2024, April 18) Embryology Male genital molecular signaling 01.jpg. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/File:Male_genital_molecular_signaling_01.jpg

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