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15. 4. 2012.

Testosterone


Testosterone is a dominant male chormone. It is located in Laydigs cells in testises.
Name androgens is used as a synonym for male sex chormone that is produced not only in testises, but in other tissues in organism. Adrenal gland secrets at least 5 various androgens, but their total male activity is so small that even at females they don’t create male features.
Testosteron rimifons and from them created anabolic steroids that are used in the purpose of doping have similarities in chemical structure, metabolism, type of effect on target tissues and unwished effects.
The most important representors of testosterone:
Natural androgens – Testosterone and metil-testosterone
Synthetic androgens – mesterolone and fluoximesterolone

Chormones chemistry and metabolism

All androgenes are steroid compositions that are synthetized from Acetil Co-A, through cholesterole to the chormone of steroid structure. The most active is testosterone.
All androgens are derivates of androstane that has steroid structure with 19 carbon atoms:

Androstane  »»»  testosterone( 17 βhydroxy- androsten–4-3-on)

After testosterone is being excreted, it circulates in blood for the most 15-30 minutes, lightly connected for plasma proteins. On this way it comes to the target tissues where it connects to proper receptors. Part that is not been used in tissues is fastly inactivated and excreted.

Testosterone  »»»  5α dihydrotestosterone(DHT)
In peripheral tissues it comes to the reduction of double connection C-4 testosterone, and DHT creates as the consequence of reaction. Near of receptor spot is found the biggest number of this metabolite, so it is thought that it is the most active.

In target tissues testosterone goes into dihydrotestosterone, and in that shape it exposes its cell effects. Dihydrotestosterone connects to receptor protein in cytoplasm, and the complex created that way difunds in the nucleus where it activates DNA transcription process. The result is specific accelerated synthesis of specific proteins in the cell.
Degradation and inactivation of testosterone is done in the liver. Testosterone goes into androsterone and dehydroepiandrosterone, and it conjugates in glucuronydes and sulphates. In that transformed shape testosterone is excreted through urine or feces.
Daily testosterone production at healthy male is approximately 8mg. Physical training, and some other factors can influent on the level of this chormone.

Testosterone metabolites – that are less active or inactive:
Testosterone » oxidation » androstenedion
Androstenedion » reduction on position 3 or 4 »
3α5α – androsterone
3α5β – etocholanolon
3β5α – epiandrosterone

In the male organism small amounts of estrogen are created. It is thought that one part of estrogene goes through the process of synthesis in intersticial testis cells, and other part is created in various tissues through testosterone transformation. Extreme high values of synthetic testosterone and anabolic steroids that are used to dope athletes probably convert to estrogen. That is probably the reason for gynecomastia at males.



Physiological effects of testosterone

·         Functions during male fetus embrional growth
·         Growth and maturation of male sex organs and secondary sexual features later during puberty and adolescence
·         Influence on nitrous retention and muscles development
·         Influence on bone growth and calcium retention
·         Increase in  basal metabolism values
·         Increase in number of erythrocytes
·         Influence on water and electrolytes balance
·         Influence on hair growth over the whole body and face at males and larynx hypertrophy(changes in voice)

Regulation of testosterone secretion

Luteinizing chormone(LH), that excretes front part of hypophisis, stimulates interstitial testis cells on production and release of testosterone. Amount of testosterone excreted is proportional to the amount of released LH.
The most important function of adenohypophysis folicostimulating chormone(FSH) is spermatogenesis regulation, or influence on the process of primary spermatocytes transformation into secondary in spermatic canals.
Hypothalamus controls excretion of gonadotropins(FSH and LH) through its own chormones that are called factors that release gonadotropins(releasing factors- Rh).
Human chorionic gonadotropine(HHG)placenta chormone has the same stimulative effects on testises like LH.

Appliance in sport

Testosteron rimifons are used in sport due to its anabolic effects on muscle tissue. All other following effects are mostly unwished in sports. These harmful effects can be extremely emphasized, and they are the result of doses that are multiply higher than therapeutically recommended.
Oral appliance of testosterone is not possible, cause if it is intaked in this way, it will be completely digested in liver, so only intramuscular use is done.
Doses that athletes use are mostly 50-200mg per day.

Detection

In the goal of doping detection it is needed to determine ratio of testosterone and its epimere – epitestosterone. In normal conditions this relation is T/E = 1:1. It is thought that recommendation of value T/E 6:1 is very suspicious to abuse of synthetic testosterone, while T/E ratio of 10:1 is treated as confirmed doping.  

“Doping in sport”, Marina Djordjevic Nikic

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