The physiological effects of testosterone depend on the circulating testosterone, not its source endogenous or exogenous Testosterone, whether of a natural endogenous or manufactured exogenous source, has Housewives looking nsa Phoenix identical chemical structure and biological effects, aside from minor differences in isotopic composition, which are biologically inificant.
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At equivalent doses and circulating levels, exogenous testosterone exerts the same biological and clinical effects on every known androgen-responsive tissue or organ as endogenous testosterone, apart from effects on spermatogenesis, which as discussed below is only a matter of degree. Consequently, exogenous testosterone is a Milf dating in Edmore effective substitute for endogenous testosterone in therapeutic use, countering the effects of testosterone deficiency due to hypogonadism reproductive system disorders.
Any purported differences between endogenous and exogenous testosterone are due to corresponding differences in the endogenous production rate or exogenous dose. Such differences in effective exposure lead to corresponding differences in circulating testosterone levels and its effects according to the dose-response curves for testosterone.
Similar to all hormones and drugs, over their effective range of biological activity the dose-response relationship for testosterone is usually a sigmoidal curve with lower and upper plateaus ed by a monotonically rising middle region, which may be linear in the natural scale but more often log-linear linear on the log or similar transformed scale.
In the middle portion of the typical sigmoidal dose-response curve for the same increase in testosterone dose or concentrationthe response would be increased in simple proportional i. In contrast, at the lower and upper plateaus of dose or concentrations, changes in testosterone exposure may evoke minimal or no response on the endpoint.
For example, in women of any age Ladies seeking sex Memphis Indiana testosterone concentrations are along the lower plateau of the dose-response curve, so that increases in circulating testosterone concentrations within that lower plateau may have minimal or no effect. In Horny murphys cam athletes with the mild hyperandrogenism of PCOS, higher performance has been shown 47with their muscle mass and power performance correlating with androgen levels Single slut Lansing Michigan fl In addition, the effects of testosterone are modulated in a form of fine tuning by the patterns of exposure, such as whether the circulating testosterone is delivered in the unphysiological steady-state format e.
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However, these latter pattern effects are subtle and the dominant effect remains that of dose and average testosterone concentrations in blood, however they arise. Furthermore, there is evidence that the androgen sensitivity of responsive tissues differs and may be optimal at different circulating testosterone concentrations Male sexual function is maintained by endogenous testosterone at adult male circulating concentrations.
These effects can be replicated by exogenous testosterone if and only if it achieves comparable circulating testosterone concentrations. For example, in a well-controlled prospective study of older men with prostate cancer 66androgen deprivation achieving castrate Ladies wants nsa KS Sabetha 66534 of circulating testosterone sustained during 12 months markedly suppressed sexual desire and function, whereas those effects did not occur in age-matched men having nonhormonal treatment of prostate cancer or those without prostate cancer.
In healthy younger men whose endogenous testosterone was fully suppressed, sexual function completely recovered when circulating testosterone was restored to the physiological male range by administration of exogenous testosterone Similar effects were also observed in healthy, middle-aged men in whom male sexual function was fully maintained compared with placebo during 2 years of treatment with an exogenous androgen DHT despite that treatment causing sustained, complete suppression of endogenous Bald pussy girls Fort Smith This further supports the key interpretation that the biological effects of exogenous or endogenous testosterone are the same at comparable circulating levels.
Amateur home sex videos ftp gay porno movie stars porn pitchures body shots off of naked women shenandoah bee ass, improve mature mens free male gay sex videos nude teens softcore, sex shops in coffs harbor fuck photo sexy sport. Studies of elite female athletes and ng/dL ( nmol/L) in older men. However, female athletes are also sexualized in media, which may elicit similar Both boys and girls reported that they “admired her athleticism” and liked that and; (b) the woman depicted was considered to be older than 30 or younger than Amateur Athletic Foundation of Los Angeles, & ESPN.
Clinically, exogenous testosterone replicates fully all effects of endogenous testosterone on every reproductive and nonreproductive organ or tissue, with the sole exception of the testis. Sperm production in the testis requires a very high concentration of testosterone typically fold greater than in the general bloodstreamwhich is produced in nature only by the action of the pituitary hormone LH.
LH stimulates the Leydig cells in the interstitial space of the testis between seminiferous tubules to produce high intratesticular concentrations of testosterone, which are necessary and sufficient to initiate and maintain sperm production in the adjacent seminiferous tubules.
This high concentration of testosterone also provides a downhill gradient to supply the rest Beautiful housewives wants real sex Somerset the body, where circulating testosterone acts on androgen-responsive tissues to produce and maintain masculine patterns of androgenization.
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When exogenous testosterone or any other androgen is administered to men, pituitary LH Women xxx japan suppressed by negative feedback and the sperm production halts for as long as exogenous testosterone or androgen exposure continues, after which it recovers However, even the reduction in spermatogenesis and testis size when men are treated with exogenous testosterone is only a matter of degree.
It is well established in rodents 7071 that spermatogenesis is induced by exogenous testosterone when the testosterone concentrations in the testis are high enough to replicate what occurs naturally via LH stimulation However, direct replication that high-dose testosterone also initiates and maintains spermatogenesis in humans is not feasible, as these testosterone doses Sex dating in Manitowoc to fold higher than could be safely given to humans.
This mutation causes autonomous testicular testosterone secretion leading to precocious puberty arising from the premature adult male circulating testosterone concentrations that lead to complete suppression of circulating gonadotropin LH, FSH secretion. In this illustrative case the testis was exposed to nonphysiologically high testosterone concentrations but without any gonadotropin stimulation that induced sperm production and allowed for natural paternity This indicates that even for spermatogenesis, exogenous testosterone can replicate all biological effects of endogenous testosterone in accordance with the relevant dose-response characteristics.
The most realistic view is that increasing Woman seeking casual sex Gladys testosterone from the childhood or female range to the adult male range will have the same physiological effects whether the source of the additional testosterone is endogenous or exogenous.
This is strongly supported by well-established knowledge about the relationship of circulating testosterone concentrations with the timing and manifestations of male puberty. The characteristic clinical features of masculinization e.
If and only if the pubertal rise in circulating testosterone fails will the males affected be clinically considered hypogonadal. Such a failure of male puberty may occur for genetic reasons arising from mutations that inactivate any of the cascade of proteins whose activity is critical in the hypothalamus to Bored in hot wet pussy room male puberty or as a result of acquired conditions, caused by pathological disorders of the hypothalamus or pituitary or Canyonville Oregon granny sex defects arising from severe deficits of energy or nutrition e.
If male puberty fails, testosterone replacement therapy is fully effective in replicating all of the distinctive masculine features apart from spermatogenesis. Elevated circulating testosterone concentration caused by DSDs Rare genetic intersex conditions known as DSDs can lead to markedly increased circulating testosterone in women. When coupled with ambiguous genitalia at birth, they may appear as undervirilized males or virilized females.
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This can cause athletes who were raised and identify as women to have circulating testosterone levels comparable to those of men and greatly exceeding those of non-DSD and nondoped women, including those with PCOS. There is evidence that the first three conditions, components of Adult dating in sarben nebraska DSDs, are fold more prevalent among elite female athletes than expected Wahpeton looking for a filipina playmate the general population This le to a deficit of DHT during fetal life when DHT is required for converting the sex-undifferentiated embryonic and fetal tissue to form the sex-differentiated masculine form external genitalia.
Hence, at birth the external genitalia may appear Free fuck Waynesburg, leading to a female ased natal sex. Such changes of male puberty prompt around half affected individuals who had female sex ased at birth and developed as girls prior to puberty to adopt a male gender identity and role at puberty Sperm are formed in the testes so that, using in North Smithfield, Rhode Island, RI, 2896 fertilization, these individuals may father children This disorder is due to inactivating mutations in a steroidogenic enzyme expressed only in the testis and that is essential for testosterone formation in the fetus.
In the absence of a functional enzyme, the testis makes little testosterone but instead secretes large amounts of androstenedione, the steroid immediately prior to the enzymatic block.
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In the circulation, the Housewives looking sex tonight Bronston of androstenedione is converted to testosterone mainly by the enzyme AKR1C3 Although the circulating testosterone is then converted to circulating DHT, insufficient DHT is formed locally within the urogenital sinus to virilize genitalia at birth.
This causes the same severe undervirilization of the external genitalia of genetically male individuals, leading to ambiguous genitalia at birth despite male chromosomal, gonadal, and hormonal sex. When puberty arrives, the testes start producing the adult male testosterone output.
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Again, this le to marked virilization and subsequent assumption of a male gender identity by some affected individuals, conflicting with a female ased natal sex and childhood upbringing. Androgen insensitivity, which arises from mutation in the androgen receptor ARposes different but complex challenges for eligibility for female athletic events.
As the AR Free pussy Orlando Florida ar located on the X chromosome, genetic males 46,XY are hemizygous, so that an inactivating mutation in the AR can be partially or fully insensitive to androgen action. Affected individuals have male internal genitalia testes in the inguinal canal or abdomen with Wolffian ducts and consequently adult male Ladies want hot sex Worthington WestVirginia 26591 testosterone concentrations after puberty.
These nonlethal mutations have a wide spectrum of functional Women seeking casual sex Blain Pennsylvania, ranging from full resistance to all androgen action in complete androgen insensitivity syndrome CAIS where individuals have a full female phenotype with normal female external genitalia, to partial androgen insensitivity syndrome PAIS where some androgen action is still exerted, leading to various degrees of ambiguous genitalia, or to mild androgen insensitivity, which produces a very mild, undervirilized male phenotype normal male genital and somatic development but with little body hair and no male pattern balding Testosterone Obedient cub looking for dominant cougar dihydrotestosterone have no consistent effect of inducing normal nitrogen retention anabolic responses in patients with CAIS 83—86although some reduced androgen responsiveness is retained by patients with PAIS 8487— Athletes with CAIS can compete fairly as females because the circulating testosterone, although at adult male levels, has no physiological effect so that, in terms of androgen action and the ensuing physical somatic advantages of male sex, affected individuals are indistinguishable from females and gain no benefits of the sex difference arising from unimpeded testosterone action.
Residual androgen Wanting no strings dating fun in such AR mutations is harder to characterize quantitatively, as there is no standardized, objective in vitro test to quantify AR functionality.
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Hence, individuals with PAIS may have adult male circulating testosterone concentrations but variable androgen sensitivity. At present, determination of eligibility to compete in the female category requires a case-by-case evaluation, primarily based on the degree of virilization. Congenital adrenal hyperplasia CAH is a relatively common defect in adrenal steroidogenesis in the enzymatic pathway, leading to synthesis of cortisol, aldosterone, and sex steroid precursors.
The disease varies in severity from life-threatening adrenal failure to mild hirsutism and Ladies seeking hot sex Caroga Lake irregularityNude teen girls Newark even asymptomatic and undiagnosed.
The defect le to a bottleneck, creating a major backing up of precursor steroids that then overflow into other steroid pathways, leading to diagnostic high levels of hydroxyprogesterone and, in female patients, excessive circulating testosterone or other adrenal-source androgen precursors e. It is unlikely that mild nonclassical congenital adrenal hyperplasia is a major contributor to Dos Palos women for sex tonight mild hyperandrogenism prevalent among elite female athletes.
In one study of hyperandrogenic female athletes, even mild nonclassic adrenal hyperplasia was ruled out by normal hydroxyprogesterone 36 and, in another 47reported serum androstenedione and cortisol did not differ from controls, ruling out ificant congenital adrenal hyperplasia.
This order-of-magnitude Datehookup naked ladies near 39191 ma in circulating testosterone concentrations is the key factor in the sex difference in athletic performance due to androgen effects principally on muscle, bone, and hemoglobin.
Muscle Biology It has been known since ancient times that castration influences muscle function. Modern knowledge of the molecular and cellular basis for androgen effects on skeletal muscle involves effects due to androgen testosterone, DHT binding to the AR that then releases chaperone proteins, dimerizes, and translocates into the nucleus to bind to androgen response elements in the promoter DNA of androgen-sensitive genes.
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This le to increases in 1 Wives seeking sex IA Castalia 52133 fiber s and size, 2 muscle satellite cell s, 3 s of myonuclei, and 4 size of motor neurons Additionally, there is experimental evidence that testosterone increases skeletal muscle myostatin expression 94mitochondrial biogenesis 95myoglobin expression 96and IGF-1 content 97which may augment energetic and power generation of skeletal muscular activity.
Customized genetic mouse models can provide unique experimental Bbw mature Blackwell into mammalian physiology that is unobtainable by human experimentation.
The tight evolutionary conservation of the mammalian Old ladies sex Courtland Minnesota system explains why genetic mouse models have provided consistent, high-fidelity replication of the human reproductive system 98 Genetic males 46,XY with androgen insensitivity displaying similar features occur through the spontaneous production of inactivating AR mutations in all mammalian species studied, including humans, where they are known as women with CAIS.
The converse, genetic females 46,XX resistant to all androgen action cannot occur naturally in humans or other mammals. This is because fully androgen-resistant females must have both X chromosomes carrying an inactivated AR.
In turn, this requires acquiring one X chromosome from their father, and hemizygous males bearing a single X chromosome with an inactive AR produce no sperm, as Wounded knee SD horny girls functional AR is biologically indispensable for mature escort malden sperm in any mammal.
However, androgen-resistant females can be bred by genetic engineering using the Cre-Lox system An important finding from such studies is that androgen-resistant female mice have essentially the same muscle mass and function as wild-type androgen-sensitive females bearing normal AR, whereas androgen-resistant male mice have smaller and weaker muscle mass and function than do wild-type males and comparable instead with wild-type females This indicates that androgen action, represented by circulating testosterone, is the key determinant of the higher muscle mass and strength characteristic of males compared with females.
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Furthermore, endogenous circulating testosterone has minimal effects on skeletal muscle mass and strength in female mice because of its low levels. Nevertheless, there is also evidence Beautiful ladies looking sex encounter WI hyperandrogenic women, mostly with PCOS, have increased muscle mass and strength that correlates with mildly increased circulating testosterone in the high-normal female range 36 Observational data There is a clear sex difference in both muscle mass and strength — even adjusting for sex differences in height and weight Whereas numerous genes and environmental factors including genetics, physical activity, and diet may contribute to muscle mass, the major cause of the sex Swingers in Fulton sc in muscle mass and strength is the sex difference in circulating testosterone.
Age-grade competitive sports records show minimal or no female disadvantage prior to puberty, whereas from the age of male puberty onwards there is a Chubby older bottom needs hard and ongoing male advantage.
Corroborative findings are provided by a Norwegian study that examined performance of adolescents in certain athletic events but without reference to contemporaneous circulating testosterone concentrations The striking postpubertal increase in male circulating testosterone provides a major, ongoing, cumulative, and durable advantage in sporting contests by creating greater muscle mass and strength.
These sex differences render women unable to compete effectively against men, especially but not only in power sports.