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BCH441 GROUP 2BIOCHEMISTRY OF

ANDGROGENS

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GROUP MEMBERSAdjekukor Ufuoma CynthiaAkpata PatrickKayode KazeemOkechukwu EmekaOrakpo AnabelUdechukwu Treasure

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CONTENTSIntroductionTypes of AndrogensTestosteroneAndrostendedioneDehydroepiandrosteroneBiosynthesis of AndrogensTransport , Metabolism and ExcretionBiochemical FunctionsClinical Disorders of Androgen SecretionConclusion

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INTRODUCTIONAndrogen is a type of sex steroid

hormone.

They are mostly produced by the Leydig cells of testes, though a smaller amount originates from the adrenal glands.

The theca cells at the periphery of the ovarian follicles also produce a small amount of androgens.

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TYPES OF ANDROGENSThey are majorly three types of the

androgens namely:

Testosterone

Androstendedione

Dehydroepiandrosterone

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TESTOSTERONEThis is the major androgen

synthesized in tetses.

It has 19 carbon atoms in its structure.

Other subsidiary sources include: adrenal cortex and the ovary.

Its plasma level is about 0.7 μg/dl in males and < 0.1 μg/dl in females.

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Testosterone

Fig. 1 Structure of testosterone

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ANDROSTENDEDIONEIt has 19 carbon atoms in its

structure.

It is synthesized primarily in the adrenal cortex.

Other, subsidiary sources include: ovary and testis.

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Androstendedione

Fig 2 Structure of androstendedione

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DEHYDROEPIANDROSTERONE

It has 19 carbon atoms in its structure.

It is primarily synthesized testis.

It can also be synthesized in adrenal cortex and the ovary

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Dehydroepiandrosterone

Fig 3 Structure of dehydroepiandrosterone

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BIOSYNTHESIS OF ANDROGENS

Cholesterol is the biosynthetic precursor of all steroid hormones, including androgens.

Pregnenolone, initially formed from cholesterol is converted to progesterone by microsomal and cytoplasmic enzyme.

13Fig. 4 Biosynthetic pathway of pregnenolone

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Biosynthesis of AndrogensPregnenolone is converted to 17-

hydroxypregnenolone by the enzyme 17- hydroxylase.

17-hydroxypregnenolone is cleaved by the enzyme 17-20 lyase to give dehydroepiandrosterone (an androgen).

Dehydroepiandrosterone is then reduced by the enzyme 3β–Hydroxysteroid dehydrogenase to yield androstendedione.

Or pregnenolone is converted to progesterone by 3β- Hydroxysteroid dehydrogenase.

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Biosynthesis of AndrogensThen the synthesis starts with the

hydroxylation of progesterone at C-17 by 17-Hydroxylase to give 17-hydroxyprogesterone .

The side chain consisting of C-20 and C-21 is then cleaved by the enzyme 17-20 Lyase to yield androstendedione (an androgen).

Testosterone, another androgen is formed by the reduction of the 17-keto group of androstendedione which is catalyzed by 17-keto-reductase.

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Fig 5 Biosynthetic pathway of dehydroepiandrosterone and androstenedione

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Fig. 6 Biosynthetic pathway of testosterone

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Biosynthesis of AndrogensTestosterone is reduced by 5α–

reductase to yield dihydrotestosterone (DHT).

It is a powerful embryonic androgen that instigates the development and differentiation of the male phenotype.

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Fig 7 Biosynthetic pathway of dihydrotestosterone

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TRANSPORT, METABOLISM AND EXCRETION

Testosterone circulates in blood in association with two proteins: sex hormone-binding globulin (SHBG) and testosterone-oestrogen-binding globulin (TEBG).

Both these proteins are formed in the liver.

The liver metabolizes androgens to 17-ketosteroids, which are excreted in urine.

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BIOCHEMICAL FUNCTIONSTestosterone promotes appearance of

secondary sexual characteristics, such as Deeping voice and masculine distribution of body hair, libido and potency.

Testosterone in association with follicle-stimulating hormone (FSH) is required for normal spermatogenesis.

Androgens promote RNA synthesis and protein synthesis thereby causing positive nitrogen balance.

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Biochemical FunctionsThe production of D-fructose from D-

glucose in seminal vesicles is increased by androgens. The androgens synthesis of aldolase, thereby enhancing glycolysis.

Androgens increase renal retention of sodium chloride and water , though to a much smaller extent than mineralocorticoids.

Androgens promote formation of bone matrix proteins.

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CLINICAL DISORDERS OF ANDROGEN SECRETION

Hypogonadism (under secretion)In primary hypogonadism, there is failure of

testes to produce testosterone.

Hypergonadism (over secretion)It is seen in precocious puberty.

A rare disorder resulting either from early maturation of the normal hypothalamo-pituitary-gonadal axis or as a result of a tumour that secretes androgen (or HCG).

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