Androgen receptor: Difference between revisions

Line 54:

=Function=

AR is expressed in many tissues, so androgens have been documented to have significant biological actions in bone, muscle, prostate, ovaries, endometrium, bladder, skin, cardiovascular, immune, neural and hematopoietic systems <ref name="Bench to Bedside" /><ref name="Above and Beyond">PMID: 29481861</ref>.

As AR is expressed in many tissues, androgens have been documented to have significant biological actions in bone, muscle, prostate, ovaries, endometrium, bladder, skin, cardiovascular, immune, neural and hematopoietic systems <ref name="Bench to Bedside" /><ref name="Above and Beyond">PMID: 29481861</ref>.

Androgens have a role in behavior and cognition in neuronal cells in the CNS <ref name="Above and Beyond" />. It has also been shown they regulate hair growth, sebum production and secretion, wound healing and cutaneous barrier formation in the skin <ref>PMID: 28912032</ref>.

The absence of AR has an impact on the fertility in granulosa cells in the ovary and it also affects the myometrial cell growth in uterine glandular epithelial cells in the endometrium <ref name="Above and Beyond" />.

Line 60:

Drugs targeting the AR has the potential to be used in prostate cancer, benign prostatic hyperplasia (BPH), osteoporosis, breast cancer, hypogonadism, conditions where cachexia is a consequence of the disease state (HIV, cancer, immobilization), urinary incontinence, muscle wasting conditions as Duchenne muscular dystrophy (DMD) and Alzheimer’s disease <ref name="SARMs knowledge">PMID: 30503797</ref><ref name="NR">PMID: 23457206</ref><ref name="SARMs therapy">PMID: 32257854</ref><ref name="SARMs">PMID: 28624515</ref>.

====Prostate Cancer====

~~Androgen receptor~~ is fundamental for the correct function, development of the prostate <ref>PMID: 12237244</ref> having a critical role in the control of homeostasis between prostate cells differentiation and proliferation <ref name="ARA prostate">PMID: 24639562</ref>. It's widely accepted ~~that androgen~~ receptor plays an important role in prostate cancer cells due to the alteration of that equilibrium, shifting the AR to a more proliferative transcriptional program <ref name="ARA prostate" />.

AR is fundamental for the correct function and development of the prostate <ref>PMID: 12237244</ref>, having a critical role in the control of homeostasis between prostate cells differentiation and proliferation <ref name="ARA prostate">PMID: 24639562</ref>. It's widely accepted this receptor plays an important role in prostate cancer cells due to the alteration of that equilibrium, shifting the AR to a more proliferative transcriptional program <ref name="ARA prostate" />.

====Alzheimer’s Disease====

Androgen depletion is considered a significant risk factor for Alzheimer’s disease and circulating testosterone levels are inversely correlated with levels of ß-amyloid (ßA) in the brains of aged men <ref name="SARMs knowledge" />.

Androgen depletion is considered a significant risk factor for Alzheimer’s disease, and circulating testosterone levels are inversely correlated with levels of ß-amyloid (ßA) in the brains of aged men <ref name="SARMs knowledge" />.

Line 68:

==Steroid==

===Natural ligand: Testosterone===

Aging and other factors are associated with a reduction of testosterone levels which could lead to late onset hypogonadism <ref name="hypogonadism">PMID: 32737921</ref>. The decrease of the ~~testosterone~~ levels and therefore its active metabolite levels (DHT) are related with several symptoms such as low libido, erectile dysfunction, skeletal muscular loss <ref name="NR" /><ref name="hypogonadism" />, increased cardiovascular risk <ref name="hypogonadism" />… To treat those symptoms is used Testosterone Restitution Therapy (TRT) which has been associated with the ~~improve~~ in sexual function, increase in muscle mass and bone mineral density <ref name="Testosterone">PMID: 34888506</ref>.

Aging and other factors are associated with a reduction of testosterone levels which could lead to late onset hypogonadism <ref name="hypogonadism">PMID: 32737921</ref>. The decrease of the T levels and therefore its active metabolite levels (DHT) are related with several symptoms such as low libido, erectile dysfunction, skeletal muscular loss <ref name="NR" /><ref name="hypogonadism" />, increased cardiovascular risk <ref name="hypogonadism" />, etc. To treat those symptoms is used Testosterone Restitution Therapy (TRT) which has been associated with the improvement in sexual function and the increase in muscle mass and bone mineral density <ref name="Testosterone">PMID: 34888506</ref>.

One of the problems associated with the use of T as a therapeutic agent in TRT ~~are~~ the delivery method, tending to have low efficacy orally administered <ref name="NR" /><ref name="SARMs therapy" /> and having some inconvenients with intramuscular injections or implants <ref name="NR" />. Also, the use of this hormone as a treatment could triggered a lot of AR widespread around the body ~~and a long~~-term ~~exposure~~ to a high dose could lead to related side effects like erythrocytosis <ref name="NR" /><ref name="SARMs therapy" />, dyslipidemia, hepatotoxicity <ref name="SARMs therapy" /> and ~~in some clinical trials it has been described~~ an increase in cardiovascular risk <ref name="hypogonadism" /><ref name="Testosterone" />.

One of the problems associated with the use of T as a therapeutic agent in TRT is the delivery method, tending to have low efficacy orally administered <ref name="NR" /><ref name="SARMs therapy" />, and having some inconvenients with intramuscular injections or implants <ref name="NR" />. Also, the use of this hormone as a treatment could triggered a lot of AR widespread around the body. Long-term exposures to a high dose could lead to related side effects like erythrocytosis <ref name="NR" /><ref name="SARMs therapy" />, dyslipidemia, hepatotoxicity <ref name="SARMs therapy" /> and an increase in cardiovascular risk <ref name="hypogonadism" /><ref name="Testosterone" />.

Due to all these problems, some institutions like the FDA warn about the safety issues related with this therapy assessing the reduction of its use <ref name="hypogonadism" /><ref name="Testosterone" />. However, other agencies like the EMA supported by the European Academy of Andrology establish the practical use of this therapy in men’s hypogonadism <ref name="hypogonadism" /><ref name="Testosterone" />. So, there is still some controversy about its use, and it’s still currently studied in clinical trials <ref name="Testosterone" />.

Androgen receptor: Difference between revisions

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@@ Line 54: / Line 54: @@
 =Function=
-AR is expressed in many tissues, so androgens have been documented to have significant biological actions in bone, muscle, prostate, ovaries, endometrium, bladder, skin, cardiovascular, immune, neural and hematopoietic systems <ref name="Bench to Bedside" /><ref name="Above and Beyond">PMID: 29481861</ref>.
+As AR is expressed in many tissues, androgens have been documented to have significant biological actions in bone, muscle, prostate, ovaries, endometrium, bladder, skin, cardiovascular, immune, neural and hematopoietic systems <ref name="Bench to Bedside" /><ref name="Above and Beyond">PMID: 29481861</ref>.
 Androgens have a role in behavior and cognition in neuronal cells in the CNS <ref name="Above and Beyond" />. It has also been shown they regulate hair growth, sebum production and secretion, wound healing and cutaneous barrier formation in the skin <ref>PMID: 28912032</ref>.
 The absence of AR has an impact on the fertility in granulosa cells in the ovary and it also affects the myometrial cell growth in uterine glandular epithelial cells in the endometrium <ref name="Above and Beyond" />.
@@ Line 60: / Line 60: @@
 Drugs targeting the AR has the potential to be used in prostate cancer, benign prostatic hyperplasia (BPH), osteoporosis, breast cancer, hypogonadism, conditions where cachexia is a consequence of the disease state (HIV, cancer, immobilization), urinary incontinence, muscle wasting conditions as Duchenne muscular dystrophy (DMD) and Alzheimer’s disease <ref name="SARMs knowledge">PMID: 30503797</ref><ref name="NR">PMID: 23457206</ref><ref name="SARMs therapy">PMID: 32257854</ref><ref name="SARMs">PMID: 28624515</ref>.
 ====Prostate Cancer====
-Androgen receptor is fundamental for the correct function, development of  the prostate <ref>PMID: 12237244</ref> having a critical role in the control of homeostasis between prostate cells differentiation and proliferation <ref name="ARA prostate">PMID: 24639562</ref>. It's widely accepted that androgen receptor plays an important role in prostate cancer cells due to the alteration of that equilibrium, shifting the AR to a more proliferative transcriptional program <ref name="ARA prostate" />.
+AR is fundamental for the correct function and development of the prostate <ref>PMID: 12237244</ref>, having a critical role in the control of homeostasis between prostate cells differentiation and proliferation <ref name="ARA prostate">PMID: 24639562</ref>. It's widely accepted this receptor plays an important role in prostate cancer cells due to the alteration of that equilibrium, shifting the AR to a more proliferative transcriptional program <ref name="ARA prostate" />.
 ====Alzheimer’s Disease====
-Androgen depletion is considered a significant risk factor for Alzheimer’s disease and circulating testosterone levels are inversely correlated with levels of ß-amyloid (ßA) in the brains of aged men <ref name="SARMs knowledge" />.
+Androgen depletion is considered a significant risk factor for Alzheimer’s disease, and circulating testosterone levels are inversely correlated with levels of ß-amyloid (ßA) in the brains of aged men <ref name="SARMs knowledge" />.
@@ Line 68: / Line 68: @@
 ==Steroid==
 ===Natural ligand: Testosterone===
-Aging and other factors are associated with a reduction of testosterone levels which could lead to late onset hypogonadism <ref name="hypogonadism">PMID: 32737921</ref>. The decrease of the testosterone levels and therefore its active metabolite levels (DHT) are related with several symptoms such as low libido, erectile dysfunction, skeletal muscular loss <ref name="NR" /><ref name="hypogonadism" />, increased cardiovascular risk <ref name="hypogonadism" />… To  treat those symptoms is used Testosterone Restitution Therapy (TRT) which has been associated with the improve in sexual function, increase in muscle mass and bone mineral density <ref name="Testosterone">PMID: 34888506</ref>.
+Aging and other factors are associated with a reduction of testosterone levels which could lead to late onset hypogonadism <ref name="hypogonadism">PMID: 32737921</ref>. The decrease of the T levels and therefore its active metabolite levels (DHT) are related with several symptoms such as low libido, erectile dysfunction, skeletal muscular loss <ref name="NR" /><ref name="hypogonadism" />, increased cardiovascular risk <ref name="hypogonadism" />, etc. To treat those symptoms is used Testosterone Restitution Therapy (TRT) which has been associated with the improvement in sexual function and the increase in muscle mass and bone mineral density <ref name="Testosterone">PMID: 34888506</ref>.
-One of the problems associated with the use of T as a therapeutic agent in TRT are the delivery method, tending to have low efficacy orally administered <ref name="NR" /><ref name="SARMs therapy" /> and having some inconvenients with intramuscular injections or implants <ref name="NR" />. Also, the use of this hormone as a treatment could triggered a lot of AR widespread around the body and a long-term exposure to a high dose could lead to related side effects like erythrocytosis <ref name="NR" /><ref name="SARMs therapy" />, dyslipidemia, hepatotoxicity <ref name="SARMs therapy" /> and in some clinical trials it has been described an increase in cardiovascular risk <ref name="hypogonadism" /><ref name="Testosterone" />.
+One of the problems associated with the use of T as a therapeutic agent in TRT is the delivery method, tending to have low efficacy orally administered <ref name="NR" /><ref name="SARMs therapy" />, and having some inconvenients with intramuscular injections or implants <ref name="NR" />. Also, the use of this hormone as a treatment could triggered a lot of AR widespread around the body. Long-term exposures to a high dose could lead to related side effects like erythrocytosis <ref name="NR" /><ref name="SARMs therapy" />, dyslipidemia, hepatotoxicity <ref name="SARMs therapy" /> and an increase in cardiovascular risk <ref name="hypogonadism" /><ref name="Testosterone" />.
 Due to all these problems, some institutions like the FDA warn about the safety issues related with this therapy assessing the reduction of its use <ref name="hypogonadism" /><ref name="Testosterone" />. However, other agencies like the EMA supported by the European Academy of Andrology establish the practical use of this therapy in men’s hypogonadism <ref name="hypogonadism" /><ref name="Testosterone" />. So, there is still some controversy about its use, and it’s still currently studied in clinical trials <ref name="Testosterone" />.