In the name of Allah,The most Beneficent,The most Merciful
Mechanism of Action ofMechanism of Action ofTestosteroneTestosterone• Most of the effects result from increasedrate of protein formation in the target cells.• studied extensively in the prostate gland,most affected by testosterone.• In this gland, testosterone enters theprostatic cells within a few minutes aftersecretion.
Mechanism of Action of TestosteroneMechanism of Action of Testosterone• The effects of testosterone occur byway of two main mechanisms:• by activation of the androgen receptorAR (directly or as DHT),• By conversion to estradiol andactivation of certain estrogenreceptors.• Free testosterone is transported intothe cytoplasm of target tissue cells,where it can bind to the androgenreceptor, or can be reduced to 5α-dihydrotestosterone (DHT) by thecytoplasmic enzyme 5-alphareductase.• The T-receptor or DHT-receptorcomplex undergoes a structuralchange that allows it to move into thecell nucleus and bind directly tospecific nucleotide sequences of thechromosomal DNA.
Mechanism of Action of TestosteroneMechanism of Action of Testosterone• The areas of binding are calledhormone response elements(HREs), Within 30 minutes,RNA has become activatedand the concentration of RNAbegins to increase in theprostatic cells;• The bones and the brain aretwo important tissues inhumans where the primaryeffect of testosterone is by wayof aromatization to estradiol. Inthe bones, estradiolaccelerates ossification ofcartilage into bone, leading toclosure of the epiphyses
Control of Male Sexual Functions by Hormones from the HypothalamusControl of Male Sexual Functions by Hormones from the Hypothalamusand Anterior Pituitary Glandand Anterior Pituitary Gland• control of sexual functions inboth male and the female beginswith secretion of gonadotropin-releasing hormone (GnRH) bythe hypothalamus• This hormone in turn stimulatesthe anterior pituitary gland tosecrete two other hormonescalled gonadotropic hormones:• (1) luteinizing hormone (LH)and• (2) follicle-stimulating hormone(FSH). In turn,• LH is the primary stimulus forthe secretion of testosterone bythe testes,• and FSH mainly stimulatesspermatogenesis.
Testosterone-Regulation of Its Production by LH.Testosterone-Regulation of Its Production by LH.• The quantity of testosteronesecreted increasesapproximately in directproportion to the amount of LHavailable.• Mature Leydig cells arenormally found in a childstestes for a few weeks afterbirth but then disappear untilafter the age of about 10years.• However, either injection ofpurified LH into a child at anyage or secretion of LH atpuberty causes testicularinterstitial cells that look likefibroblasts to evolve intofunctioning Leydig cells.
Negative Feedback Control of Testosterone SecretionNegative Feedback Control of Testosterone Secretion• The testosterone secreted by the testesin response to LH has the effect ofinhibiting anterior pituitary secretion of LH• Most of this inhibition results from a directeffect of testosterone on thehypothalamus to decrease the secretionof GnRH.• This in turn causes a correspondingdecrease in secretion of both LH andFSH by the anterior pituitary, and thedecrease in LH reduces the secretion oftestosterone by the testes.• Thus, whenever secretion of testosteronebecomes too great, this automaticnegative feedback effect, operatingthrough the hypothalamus and anteriorpituitary gland, reduces the testosteronesecretion back toward the desiredoperating level.• Conversely, too little testosterone allowsthe hypothalamus to secrete largeamounts of GnRH, with a correspondingincrease in anterior pituitary LH and FSHsecretion and consequent increase intesticular testosterone secretion.
Regulation of Spermatogenesis by FSH and TestosteroneRegulation of Spermatogenesis by FSH and Testosterone• FSH binds with specific FSHreceptors attached to theSertoli cells.• This causes these cells togrow and secrete variousspermatogenic substances.• testosterone (anddihydrotestosterone) also hasa strong tropic effect onspermatogenesis.• Thus, to initiatespermatogenesis, both FSHand testosterone arenecessary.
Negative Feedback Control of Seminiferous Tubule ActivityNegative Feedback Control of Seminiferous Tubule Activity• When the seminiferoustubules fail to producesperm, secretion of FSH bythe anterior pituitary glandincreases markedly.• Conversely, whenspermatogenesis proceedstoo rapidly, pituitary secretionof FSH diminishes. Thecause of this negativefeedback effect on theanterior pituitary is believedto be secretion by the Sertolicells of still another hormonecalled inhibin This hormonehas a strong direct effect onthe anterior pituitary gland toinhibit the secretion of FSHand possibly a slight effecton the hypothalamus toinhibit secretion of GnRH.
InhibinInhibin• Inhibin is a glycoprotein, like both LH and FSH,having a molecular weight between 10,000 and30,000. It has been isolated from cultured Sertolicells.• Its potent inhibitory feedback effect on theanterior pituitary gland provides an importantnegative feedback mechanism for control ofspermatogenesis, operating simultaneously withand in parallel to the negative feedbackmechanism for control of testosterone secretion.
Male Adult Sexual Life and Male ClimactericMale Adult Sexual Life and Male Climacteric• After puberty, gonadotropichormones are produced by themale pituitary gland for theremainder of life, andspermatogenesis continues untildeath.• Most men, slowly decreasingsexual functions in their late 40s or50s, and one study showed thatthe average age for terminatingintersexual relations was 68,• Decline in sexual function isrelated to decrease in testosteronesecretion,• Decrease in male sexual functionis called the male climacteric.Occasionally the male climactericis associated with symptoms ofhot flashes, suffocation, andpsychic disorders similar to themenopausal symptoms of thefemale.• These symptoms can beabrogated by administration oftestosterone, synthetic androgens,or even estrogens that are usedfor treatment of menopausalsymptoms in the female.
Gonadotropin Secreted by the Placenta During Pregnancy StimulatesGonadotropin Secreted by the Placenta During Pregnancy StimulatesTestosterone Secretion by the Fetal TestesTestosterone Secretion by the Fetal Testes• During pregnancy, thehormone human chorionicgonadotropin (hCG) issecreted by the placenta, andit circulates both in the motherand in the fetus. This hormonehas almost the same effectson the sexual organs as LH.• During pregnancy, if the fetusis a male, hCG from theplacenta causes the testes ofthe fetus to secretetestosterone. This testosteroneis critical for promotingformation of the male sexualorgans
Puberty and Its OnsetPuberty and Its Onset• During childhood the hypothalamus simply doesnot secrete significant amounts of GnRH. One ofthe reasons for this is that, during childhood, theslightest secretion of any sex steroid hormonesexerts a strong inhibitory effect on hypothalamicsecretion of GnRH.• Yet, for reasons still not understood, at the timeof puberty, the secretion of hypothalamic GnRHbreaks through the childhood inhibition, andadult sexual life begins.
Abnormalities of Male Sexual FunctionAbnormalities of Male Sexual Function• Prostate Gland and Its Abnormalities• The prostate gland remains small throughoutchildhood and begins to grow at puberty underthe stimulus of testosterone.• This gland reaches an almost stationary size bythe age of 20 years and remains at this size upto the age of about 50 years.• At that time, in some men it begins to involutes,along with decreased production of testosteroneby the testes.
Benign prostatic fibroadenomaBenign prostatic fibroadenoma• A benign prostatic fibroadenomafrequently develops in the prostate inmany older men and can cause urinaryobstruction.• This hypertrophy is caused not bytestosterone but instead by abnormalovergrowth of prostate tissue itself.
Cancer of the prostate glandCancer of the prostate gland• Cancer of the prostate gland is a common cause ofdeath, accounting for about 2 to 3 per cent of all maledeaths.• Once cancer of the prostate gland does occur, thecancerous cells are usually stimulated to more rapidgrowth by testosterone and are inhibited by removal ofboth testes so that testosterone cannot be formed.• Prostatic cancer usually can be inhibited byadministration of estrogens.• Even some patients who have prostatic cancer that hasalready metastasized to almost all the bones of the bodycan be successfully treated for a few months to years byremoval of the testes, by estrogen therapy, or by both;after this therapy the metastases usually diminish in sizeand the bones partially heal.• This treatment does not stop the cancer but does slow itand sometimes greatly diminishes the severe bone pain.
Hypogonadism in the MaleHypogonadism in the Male• When the testes of a male fetus arenonfunctional during fetal life, none of themale sexual characteristics develop in thefetus.• Instead, female organs are formed. Thereason for this is that the basic geneticcharacteristic of the fetus, whether male orfemale, is to form female sexual organs ifthere are no sex hormones.
EunuchismEunuchism• When a boy loses his testes before puberty, a state ofeunuchism ensues in which he continues to haveinfantile sex organs and other infantile sexualcharacteristics throughout life.• The height of an adult eunuch is slightly greater than thatof a normal man because the bone epiphyses are slowto unite, although the bones are quite thin and themuscles are considerably weaker than those of a normalman.• The voice is childlike, there is no loss of hair on thehead, and the normal adult masculine hair distribution onthe face and elsewhere does not occur.
• When a man is castrated after puberty, some ofhis male secondary sexual characteristics revertto those of a child and others remain of adultmasculine character.• The sexual organs regress slightly in size but notto a childlike state, and the voice regresses fromthe bass quality only slightly.• Conversely, there is loss of masculine hairproduction, loss of the thick masculine bones,and loss of the musculature of the virile male.
• in a castrated adult male, sexual desires aredecreased but not lost, provided sexual activitieshave been practiced previously.• Erection can still occur as before, although withless ease, but it is rare that ejaculation can takeplace, primarily because the semen-formingorgans degenerate and there has been a loss ofthe testosterone-driven psychic desire.
Adiposogenital syndromeAdiposogenital syndrome• Some instances ofhypogonadism are caused bya genetic inability of thehypothalamus to secretenormal amounts of GnRH.• This is associated withabnormality of the feedingcenter, causing the person togreatly overeat.• Consequently, obesity occursalong with eunuchism.• the condition is calledadiposogenital syndrome,Fröhlichs syndrome, orhypothalamic eunuchism.
Testicular Tumors and Hypergonadism in the MaleTesticular Tumors and Hypergonadism in the Male• Interstitial Leydig cell tumors develop in rare instances inthe testes, produce as much as 100 times the normalquantities of testosterone.• When such tumors develop in young children, theycause rapid growth of the musculature and bones butalso cause early uniting of the epiphyses, so that theeventual adult height actually is considerably less thanthat which would have been achieved otherwise.• Such interstitial cell tumors also cause excessivedevelopment of the male sexual organs, all skeletalmuscles, and other male sexual characteristics.