Biosintesis dan

Mekanisme Kerja
Hormon Reproduksi Pria
Kuliah 3
Rahmatina B. Herman
Bagian Fisiologi
Fakultas Kedokteran Universitas Andalas

Testes
Perform dual function of producing sperm and
secreting testosterone
80% of testicular mass consists of highly coiled
seminiferous tubules spermatogenesis
Leydig cells/ interstitial cells
- in connective tissue between seminiferous tubules
- are endocrine cells that produce testosterone
- Less easily destroyed (by x-ray, excessive heat)

Thus, portion of testes that produce sperm and

portion that secrete testosterone are distinct
structurally and functionally

Androgen
Steroid hormones

Derived from cholesterol precursor molecule

Masculinizing effects
Produced by:

Consists of:

- Testes
- Adrenal glands
- Ovary
- Testosterone
- Dihydrotestosterone
- Androstenedione

Biosynthesis of Testosterone
Testosterone, principal hormone of testis, is a
steroid
It is synthesized in:
- the Leydig cells from cholesterol
- the adrenal cortex from androstenedione
The biosynthetic pathways in all endocrine organs
that form steroid hormones are similar, the organs
differing only in the enzyme systems they contain
The enzyme in the Leydig cells is 17-hydorxylase,
while in adrenal cortex is 11- and 21 hydroxylases

Biosynthesis of Testosterone..
In the Leydig cells:
- Pregnenolone that synthesized from cholesterol
is hydroxylated in the 17 position by 17hydorxylase to form dehydroepiandrosterone

- Androstenedione is formed via progesterone and

17-hydrxyprogesterone, but this pathway is less
prominent in humans
- Dehydroepiandrosterone and androstenedione
are then converted to testosterone

Secretion of Testosterone
Testosterone secretion rate is 4-9 mg/d or 13.9-31.33
mol/d
Small amounts of testosterone are also secreted in the
females, with the major source being the ovary, possibly
also from adrenal
The secretion of testosterone is under the control of LH
The mechanism by which LH stimulates the Leydig cells
involves increased formation of cAMP via G proteincoupled LH receptor and Gs, then cAMP increases the
formation of cholesterol from cholesteryl esters and the
conversion of cholesterol to pregnenolone via the
activation of protein kinase

The formulas of the precursor steroids. Although the main secretory product of
Leydig cells is testosterone, some of precursors also enter the circulation

Secretion of Testosterone..
Once produced:
- Some of testosterone is secreted into
circulation, where it is transported to its
target sites of action
- A substantial portion goes into the lumen of
seminiferous tubules, where it plays an
important role in sperm production

Transport of Testosterone
In circulation, testosterone primarily bound to plasma
protein:
- Loosely bound with plasma albumin (33%)
- More tightly bound with a beta globulin gonadal steroid
binding globulin (GBG) (65%)

Plasma testosterone level (free and bound) is 300-1000

ng/dl in adult men, 30-70 ng/dl in adult women

It decline somewhat with age in males

Become fixed to the tissues (converted into
dihydrotestosterone) especially target organs:
- prostate gland
- external genitalia of fetal male

Plasma testosterone levels at various ages in human males

Metabolism of Testosterone
The testosterone that dose not become fixed to the
tissues is rapidly converted (mainly by the liver) into:
> androsterone
> dehydroepiandrosterone

conjugated as glucoronide or sulfate

excreted into
- gut in the liver bile
- urine through the kidney
> estradiol (a small amount)

Effects of Testosterone
Responsible for the distinguishing characteristics
of the masculine body
Most of testosterones actions ultimately function
to ensure delivery of sperm to the female
The effects can be group into 5 categories:
1. Effects on reproductive system before birth/ during
fetal life
2. Effects on sex-specific tissues after birth
3. Other reproduction-related effects
4. Effects on secondary sexual characteristics
5. Non reproductive actions

.Effects of Testosterone
1. Before birth/ During fetal life
- Stimulated by placental chorionic gonadotropin/
human chorionic gonadotropin (HCG)
- Secreted by genital ridges/ fetal testes

- Responsible for:
> Masculinizes reproductive tract and external
genitalia
> Promotes descent of testes into scrotum

.Effects of Testosterone
2. After birth
- Until puberty:
> Testosterone secretion ceases
> Reproductive system remain small and
nonfunctional

- At Puberty:
> Leydig cells start secreting testosterone once
again, stimulated by pituitary gonadotropin
hormone through the brain-testicular axis
> Testosterone is responsible for growth and
maturation of entire male reproductive system

.Effects of Testosterone
2. After birth
- At Puberty:
> Promotes growth and maturation of
reproductive system: testes , penis, scrotum
enlarge 8 X before the age of 20 years
> Essential for producing sperm (spermatogenesis)
> Maintains reproductive tract throughout
adulthood
Once initiated at puberty, testosterone secretion
and spermatogenesis occur continuously
throughout the males life

.Effects of Testosterone
2. After birth
- Puberty:
> Usually begin between 10 - 14 years of age (2 years
earlier in female)
> Lasting 3 - 5 years
> Period of arousal and maturation of previously
nonfunctional reproductive system
> Culminating in sexual maturity & ability to produce
> Encompasses a complex sequence of endocrine,
physical, and behavioral events
Adolescence is a broader concept that refers to entire
transition period between childhood and adulthood not
just to sexual maturation

Changes in plasma hormone concentrations during puberty in boys

Changes at puberty in boys (male secondary characteristics)

Effects of Testosterone.
2. After birth..
- Testicular efficiency gradually declines after 45 50
years of age, even though men in their 70s and
beyond may continue to enjoy an active sex life,
and some even father a child at this late age
- The gradual reduction in circulating testosterone
levels and in sperm production:
> is not caused by a decrease in testis stimulation
> probably arises from degenerative changes that occur
in small testicular blood vessels

- This gradual decline is termed male menopause/

andropause, recently has been more aptly termed
androgen deficiency in aging males (ADAM)

Effects of Testosterone..
3. Other reproduction-related effects
- Develop sexual libido and sex drive
> Important for facilitating delivery of sperm to females
> In humans, libido is also influenced by many
interacting social and emotional factors
> Once libido has developed, testosterone is no longer
absolutely required for its maintenance
In castrated males: often remain sexually active, but
at a reduced level, even though sex organ regress in
size and function

- Control gonadotropin hormone secretion through

negative-feedback mechanism

Postulated interrelationships between

the hypothalamus, anterior pituitary, and testis

Effects of Testosterone..
4. On secondary sexual characteristic..
- Effect on skin:
> Increases the thickness of the skin
> Increases the ruggedness of the subcutaneous
tissues

- Effect on muscle:
> Promotes muscle growth responsible for male
body configuration
> 50% increases in muscle over in the female
> as a result of protein deposition

Effects of Testosterone..
- Effect on hair:
Induces male pattern of hair growth:
> on face: beard
> chest hair: over the pubis and upward to linea alba
> on the back
> in genetically predisposed men: baldness

- Effect on voice:
Causes voice to deepen: typical adult masculine
bass voice
> as results of hypertrophy of the laryngeal mucosa;
enlargement of larynx; and thickening of vocal
folds

Effects of Testosterone..
5. Non reproductive actions
- Anabolic effect
Androgens increase the synthesis and decrease the
breakdown of protein increase the rate of growth

Secondary to their anabolic effects, androgen cause

moderate Na+, K+, H2O, Ca2+, SO4-, and PO4- retention,
and also increase the size of kidney
Doses of exogenous testosterone that exert significant
anabolic effects are also masculinizing and increase
libido which limits its usefulness as an anabolic agent
steroids in patients with wasting diseases

Effects of Testosterone..
5. Non reproductive actions
- Exerts a protein anabolic effect
> Increases basal metabolism (15%)
> Increases the number of red blood cells (15 - 20%)

- Promotes bone growth

> Increases total quantity of bone matrix and
deposition of calcium salts
> Deposit additional calcium salts thickness
> Specific effect on the pelvis

- Closes the epiphyseal plates

> after being converted to estrogen by aromatase

Effects of Testosterone..
- Effect on electrolyte & water balances:
> Increases the reabsorption of Na in the distal
tubules of the kidneys (only the minor degree in
comparison with adrenal mineralocortocoids)
increases volumes of extracellular fluid

- Effect on sebaceous glands:

> Increases the rate of sebaceous secretion acne

- May induced aggressive behavior

> It is unclear to what extent general behavioral
differences between the sexes are hormonally
induced or result from social conditioning

Basic Intracellular Mechanism of Action

Increases the rate of protein formation in target
cells
- Studied extensively in the prostate glands
Testosterone enter the cells
Intracellular 5-reductase
Dihydrotestosterone
Binds with a cytoplasmic receptor protein

Migrates to the nucleus

Binds with a nuclear protein

Induces the DNA RNA transcription process

Basic Intracellular Mechanism of Action..

Induces the DNA RNA transcription process

RNA polymerase become activated

Increases the concentration of RNA

Progressive increased in cellular protein

Several days
Increases the quantity of DNA

Increases number of cells

Basic Intracellular Mechanism of Action..

Some target tissues that do not have the
reductase enzyme

Testosterone cannot be changed into

dihydrotestosterone

Testosterone functions directly

The potency to induce cellular protein

formation only half

Congenital 5-Reductase Deficiency

It produces male pseudo-hermaphroditism syndrome
Individuals with this syndrome:
- Born with male internal genitalia including testis,
but have female external genitalia and are usually
raised as girls
- When reach puberty, LH secretion and circulating
testosterone levels are increased develop male
body contours and male libido
At this point, they usually change their gender
identities and become boys
The clitoris enlarge some of them can have
intercourse with women

Schematic diagram of the actions of testosterone (solid arrows)

and dihydrotestosterone (dashed arrows)

Estrogen in Males
Small amount of estrogen produced by adrenal
cortex and in adipose tissue
A portion of testosterone secreted by testes is
converted to estrogen outside testes by
enzyme aromatase, which is widely distributed
- because of this conversion, sometimes difficult to
distinguish effects of testosterone itself and
testosterone-turned-estrogen inside cells
> scientists recently learned that closure of epiphyseal
plates in males is induced not by testosterone per se
but by testosterone-turned-estrogen

Estrogen in Males..
Estrogen receptors have been identified in:
- testes
- prostate
- bone, and elsewhere

Recent findings suggest that estrogen plays an

essential role in male reproductive health
- important in spermatogenesis
- surprisingly contributes to male heterosexuality

Likely contributes to bone homeostasis

The depth, breadth, and mechanisms of action of
estrogen in males are only beginning to be explored

Tugas
Hiperaktivitas:
- Hormon seks pria pada pria
- Hormon seks wanita pada pria