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An androgen is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes the embryological development of the primary male sex organs, and the development of male secondary sex characteristics at puberty. Androgens are synthesized in the testes, the ovaries, and the adrenal glands.
Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral in shape and have a large, prominent nucleus, an eosinophilic cytoplasm, and numerous lipid-filled vesicles.
Sertoli–Leydig cell tumour is a group of tumors composed of variable proportions of Sertoli cells, Leydig cells, and in the case of intermediate and poorly differentiated neoplasms, primitive gonadal stroma and sometimes heterologous elements.
Sex cord–gonadal stromal tumour is a group of tumours derived from the stromal component of the ovary and testis, which comprises the granulosa, thecal cells and fibrocytes. In contrast, the epithelial cells originate from the outer epithelial lining surrounding the gonad while the germ cell tumors arise from the precursor cells of the gametes, hence the name germ cell. In humans, this group accounts for 8% of ovarian cancers and under 5% of testicular cancers. Their diagnosis is histological: only a biopsy of the tumour can make an exact diagnosis. They are often suspected of being malignant prior to operation, being solid ovarian tumours that tend to occur most commonly in post menopausal women.
Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.
The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is primarily present in steroid-producing cells, including theca cells and luteal cells in the ovary, Leydig cells in the testis and cell types in the adrenal cortex.
Cholesterol side-chain cleavage enzyme is commonly referred to as P450scc, where "scc" is an acronym for side-chain cleavage. P450scc is a mitochondrial enzyme that catalyzes conversion of cholesterol to pregnenolone. This is the first reaction in the process of steroidogenesis in all mammalian tissues that specialize in the production of various steroid hormones.
The steroidogenic factor 1 (SF-1) protein is a transcription factor involved in sex determination by controlling the activity of genes related to the reproductive glands or gonads and adrenal glands. This protein is encoded by the NR5A1 gene, a member of the nuclear receptor subfamily, located on the long arm of chromosome 9 at position 33.3. It was originally identified as a regulator of genes encoding cytochrome P450 steroid hydroxylases, however, further roles in endocrine function have since been discovered.
WNT4 is a secreted protein that, in humans, is encoded by the WNT4 gene, found on chromosome 1. It promotes female sex development and represses male sex development. Loss of function may have consequences, such as female to male sex reversal.
Lymphotoxin-alpha (LT-α) formerly known as tumor necrosis factor-beta (TNF-β) is a protein that in humans is encoded by the LTA gene. Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines. As a cytotoxic protein, LT-α performs a variety of important roles in immune regulation depending on the form that it is secreted as. Unlike other members of the TNF superfamily, LT-α is only found as a soluble homotrimer, when found at the cell surface it is found only as a heterotrimer with LTβ.
5-Hydroxyeicosatetraenoic acid (5-HETE, 5(S)-HETE, or 5S-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. It is produced by diverse cell types in humans and other animal species. These cells may then metabolize the formed 5(S)-HETE to 5-oxo-eicosatetraenoic acid (5-oxo-ETE), 5(S),15(S)-dihydroxyeicosatetraenoic acid (5(S),15(S)-diHETE), or 5-oxo-15-hydroxyeicosatetraenoic acid (5-oxo-15(S)-HETE).
Transcription factor Sp7, also called osterix (Osx), is a protein that in humans is encoded by the SP7 gene. It is a member of the Sp family of zinc-finger transcription factors It is highly conserved among bone-forming vertebrate species It plays a major role, along with Runx2 and Dlx5 in driving the differentiation of mesenchymal precursor cells into osteoblasts and eventually osteocytes. Sp7 also plays a regulatory role by inhibiting chondrocyte differentiation maintaining the balance between differentiation of mesenchymal precursor cells into ossified bone or cartilage. Mutations of this gene have been associated with multiple dysfunctional bone phenotypes in vertebrates. During development, a mouse embryo model with Sp7 expression knocked out had no formation of bone tissue. Through the use of GWAS studies, the Sp7 locus in humans has been strongly associated with bone mass density. In addition there is significant genetic evidence for its role in diseases such as Osteogenesis imperfecta (OI).
Inhibin, beta B, also known as INHBB, is a protein which in humans is encoded by the INHBB gene. INHBB is a subunit of both activin and inhibin, two closely related glycoproteins with opposing biological effects.
A Sertoli cell tumour, also Sertoli cell tumor, is a sex cord–gonadal stromal tumour of Sertoli cells. They can occur in the testis or ovary. They are very rare and generally peak between the ages of 35 and 50. They are typically well-differentiated and may be misdiagnosed as seminomas as they often appear very similar.
Leydig cell tumour, also Leydig cell tumor, (testicular) interstitial cell tumour and (testicular) interstitial cell tumor, is a member of the sex cord-stromal tumour group of ovarian and testicular cancers. It arises from Leydig cells. While the tumour can occur at any age, it occurs most often in young adults.
START is a lipid-binding domain in StAR, HD-ZIP and signalling proteins. The archetypical domain is found in StAR, a mitochondrial protein that is synthesized in steroid-producing cells. StAR initiates steroid production by mediating the delivery of cholesterol to the first enzyme in the steroidogenic pathway. The START domain is critical for this activity, perhaps through the binding of cholesterol. Following the discovery of StAR, 15 START-domain-containing proteins were subsequently identified in vertebrates as well as other that are related.
ZNF703 is a gene which has been linked with the development of breast cancers. ZNF703 is contained within the NET/N1z family responsible for regulation of transcription essential for developmental growth especially in the hindbrain. Normal functions performed by ZNF703 include adhesion, movement and proliferation of cells. ZNF703 directly accumulates histone deacetylases at gene promoter regions but does not bind to functional DNA.
Vassilios Papadopoulos, DPharm, PhD, DSc (hon), born February 18, 1961, in Athens, Greece, is a scholar, researcher, inventor, professor, and university administrator who has served as dean of the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences at the University of Southern California in Los Angeles, California, since 2016. Previously, he was the associate vice president and director of the Biomedical Graduate Research Organization at Georgetown University from 2005 to 2007, and the executive director and chief scientific officer of the Research Institute of the McGill University Health Center from 2007 to 2015.
Steroidogenic acute regulatory protein is a protein that in humans is encoded by the STAR gene.
References
- ↑ Rahman, Nafis A; Huhtaniemi, Ilpo T (30 December 2004). "Testicular cell lines". Mol Cell Endocrinol . 228 (1–2): 53–65. doi:10.1016/j.mce.2003.05.001. PMID 15541572.
- ↑ ASCOLI, MARIO (1 Jan 1981). "Characterization of several clonal lines of cultured Leydig tumor cells: gonadotropin receptors and steroidogenic responses". Endocrinology . 108 (1): 88–95. doi: 10.1210/endo-108-1-88 . PMID 6257492.
- ↑ Zirkin BR, Papadopoulos V (2018). "Leydig cells: formation, function, and regulation". Biology of Reproduction . 99 (1): 101–11. doi:10.1093/biolre/ioy059. PMC 6044347 . PMID 29566165.