Sexual dimorphism through androgen signaling; from external genitalia to muscles

Abstract

Sexual dimorphisms can be seen in many organisms with some exhibiting subtle differences while some can be very evident. The difference between male and female can be seen on the morphological level such as discrepancies in body mass, presence of body hair in distinct places, or through the presence of specific reproductive structures. It is known that the development of the reproductive structures is governed by hormone signaling, most commonly explained through the actions of androgen signaling. The developmental program of the male and female external genitalia involves a common anlage, the genital tubercle or GT, that later on develop into a penis and clitoris, respectively. Androgen signaling involvement can be seen in the different tissues in the GT that express Androgen receptor and the different genes that are regulated by androgen in the mesenchyme and endoderm component of the GT. Muscles are also known to be responsive to androgen signaling with male and female muscles exhibiting different capabilities. However, the occurrence of sexual dimorphism in muscle development is unclear. In this minireview, a summary on the role of androgen in the sexually dimorphic development of the genital tubercle was provided. This was used as a framework on analyzing the different mechanism employed by androgen signaling to regulate the sexual dimorphism in muscle development.

Sex differences in musculoskeletal injury and disease risks across the lifespan: Are there unique subsets of females at higher risk than males for these conditions at distinct stages of the life cycle?

“…Some of such changes can be cell and tissue-specific and are potentially due to methylation of the receptor genes ( Penolazzi et al, 2004 ; Tsuboi et al, 2017 ). Cells from tissues of both males and females express sex hormone receptors ( Liu et al, 1996 ; Sciore et al, 1998 ; Yu et al, 2001 ) and both sexes make and respond to both estrogens and testosterone ( Hammes and Levin, 2019 ; Ipulan-Colet, 2022 ). Some tissues may express different levels of estrogen receptors (ER-alpha, ER-beta, plasma membrane-associated variants) and androgen receptors ( Petersen et al, 1998 ; Pujol et al, 1998 ; Walters and Nemere, 2004 ; Song and Santen, 2006 ; Chang et al, 2013 ; Madeira et al, 2013 ).…”

Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development

“…The androgen receptor (AR) has a dominant role in mammalian physiology from early development, where it is critical in establishing the male phenotype, to post-natal development and adult maintenance of multiple tissues [ 1 , 2 , 3 , 4 ]. While expressed in most cells, this ligand-regulated transcription factor is dependent on androgen (e.g., testosterone or dihydrotestosterone (DHT)) binding for activation [ 5 , 6 ].…”