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Androgen Receptor in Health and Disease
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Topic review
Updated time: 30 Jun 2021
Submitted by: Somenath Ghosh
Definition: Cannabis sativa is a cheap hallucinating agent used in different parts of the world from time unknown as a part of various religious as well as social practices. Cannabis which is a special type of Marijuana can provide temporary relief from analgesia, body pain and in some other clinical conditions. But, impacts of Cannabis on reproductive health of males and females are multi-faceted and differentially fatal. In males, Cannabis can cause changes in testicular morphology, sperm parameters (in terms of semen quality, sperm morphology, sperm mortality and sperm motility), male reproductive hormones and finally causing reduced libido. In females, Cannabis can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Current research suggest that cannabis may negatively impact on male and female fertility conditions. However, male sterility considering the Cannabis impact is totally lacking in human as well as in sub-human primates. However, very limited studies are available on Cannabis effect on primate female reproduction considering Rhesus monkeys. Hence, further studies are needed to validate that robust findings in animal models will carry over into human experience.
Topic review
Updated time: 19 Feb 2021
Submitted by: Silvano Bertelloni
Definition: Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes.
Topic review
Updated time: 05 Jul 2021
Submitted by: Antonio Di Zazzo
Definition: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hormones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical manifestation as dry eye disease. This local dryness is part of the breast cancer iatrogenic dryness, which affects overall mucosal tissue in the fragile population of those with breast cancer.
Topic review
Updated time: 16 Jul 2021
Submitted by: Kenichi Takayama
Definition: Although inhibition of the androgen–androgen receptor (AR) axis effectively represses the growth of prostate cancer, most of all cases eventually become castration-resistant prostate cancers (CRPCs). Enhancement of the expression of AR and its variants along with the downstream signals is important for disease progression. AR-V7, a constitutive active form of AR, is generated as a result of RNA splicing. RNA splicing creates multiple transcript variants from one pre-messenger RNA (mRNA) by removing introns/exons to allow mRNA translation. The molecular mechanisms leading to marked increases of AR and generation of AR-V7 have been unclear. However, recent papers highlighted the roles of RNA splicing factors which promote AR expression and production of variants. Notably, a broad range of splicing components were aberrantly regulated in CRPC tissues. Interestingly, expression of various spliceosome genes is enhanced by RNA-binding protein splicing factor proline- and glutamine-rich (PSF/SFPQ), leading to changes in the expression of AR transcript variants. Moreover, inhibition of several splicing factors repressed tumor growth in vivo. Altered expression of splicing factors is correlated to biochemical recurrence in prostate cancer patients.
Topic review
Updated time: 16 Jun 2021
Submitted by: Patrizia Limonta
Definition: Understanding the molecular mechanisms underlying prostate cancer (PCa) progression towards its most aggressive, castration-resistant (CRPC) stage is urgently needed to improve the therapeutic options for this almost incurable pathology. Interestingly, CRPC is known to be characterized by a peculiar hormonal landscape. It is now well established that the androgen/androgen receptor (AR) axis is still active in CRPC cells. The persistent activity of this axis in PCa progression has been shown to be related to different mechanisms, such as: intratumoral androgen synthesis, AR amplification and mutations, AR mRNA alternative splicing, increased expression/activity of AR-related transcription factors and coregulators. A deeper clarification of the expression and activities of the androgen/AR axis in the CRPC stage will likely lead to the identification of novel predictive biomarkers as well as to the improvement of the therapeutical options for this almost untreatable disease, in terms of precision medicine.