Male sex hormones

Male sex hormones

 Various steroids with androgenic activity are produced in

the testis .
 The main one is testosterone, which is synthesized in
Leydig or interstitial cells.
 Besides testosterone, the testis secretes a more potent
androgen [dihydrotestosterone (DHT)] and two weaker
ones (dehydroepiandrosterone and androstenedione).
 In addition, Leydig cells produce small amounts of
estradiol, estrone, pregnenolone, progesterone, 17 α-
hydroxypregnenolone, and 17-α- hydroxyprogesterone.
 Steroidogenesis

 Steroidogenesis starts in the fetus between 8 and 18

weeks of gestation, a period in which androgens play
a critical role in the development of the male
reproductive tract.
 Testosterone levels fall after birth and remain low
until puberty.
 At the onset of puberty, pituitary LH production is
activated. LH binds to receptors on Leydig cells and
stimulates testosterone synthesis and secretion.
 Testosterone levels are maintained during adult life,
with a gradual decline at older ages.
 Androgens and FSH target Sertoli cells and stimulate
the production of various polypeptides, including
inhibin, which represses, and activin, which
stimulates FSH secretion in the pituitary gland,
various cytokines, and the androgen-binding
protein that carries sex hormones in plasma.
 The androgen-binding protein ensures maintenance
of high testosterone levels within the testis.
 Sertoli cells have aromatase that catalyzes the
conversion of testosterone to estrogens.
 Questions

 Which is main male sex hormone synthesized in Leydig

cells?
 Which hormones synthesized in Leydig cells also?
 When starts steroidogenesis and when ends?
 On which cells have an action FSH (folliculo stimulated
hormone)
 On which cells have an action LH (Luteinizing hormone)
 What is function of activin?
 What is function of inhibin?
 What is function of aromathase?
 Testosterone biosynthesis.

 Testosterone is produced from cholesterol

 Almost half of the cholesterol in testis is synthesized
de novo by the Leydig cells; the rest is taken up from
plasma LDL by receptor-mediated endocytosis
 In a first step, cholesterol, of 27 carbons, is converted
into pregnenolone (21 carbons), by the multienzyme
complex 20,22-desmolase, located in mitochondria.
 From pregnenolone there are two alternative
pathways:
 the first leads to the formation of progesterone, 17-α-OH-
progesterone, androstenedione, and testosterone.
 The second results in 17-α-OHpregnenolone,
dehydroepiandrosterone, androstenediol, and testosterone
production
 Questions

 Where from synthesis testosterone?

 How many pathways do you know for conversion of
testosterone?
 Binding plasma proteins

 A normal adult testis secretes between 4 and 12 mg of

testosterone/day.
 The hormone passes to the blood, where it is transported
bound to proteins.
 Approximately 60% of circulating androgens bind with
high affinity to a sex steroidbinding β globulin.
 Almost 40% of testosterone binds to other proteins,
mainly albumin, with lower affinity, but larger transport
capacity for the hormone.
 Only a small portion (less than 2%) of the blood
androgen remains free and rapidly passes through cell
membranes and is the biologically active form.
 Synthesis regulation

 Testosterone synthesis and secretion is activated by

the ICSH (interstitial cell stimulating hormone) or
LH of adenohypophysis FSH also has an important
role in testicular function.
 It helps to increase the weight of the testis and
stimulates spermatogenesis, but not androgen
production.
 When blood testosterone level increases, there is an
inhibitory effect on ICSH secretion by negative
feedback.
 Regulation

CONTROL OF
MALE SEXUAL
FUNCTIONS BY
HORMONES
FROM THE
HYPOTHALAMS
AND ANTERIOR
PITUITARY
GLAND
 Questions

 Which plasma protein binds testosterone after

secretion?
 How regulates testosterone and sperm secretion?
 Metabolism.

 Testosterone can be converted to DHT and

estrogens.
 These transformations occur in the testis and, to a
greater extent, in other tissues, catalyzed by 5α-
reductase, NADPH dependent.
 This enzyme is found mainly in liver, skin (hair
follicles).
 Mechanism of action.

 Both testosterone and DHT freely cross cellular

membranes and reach their receptor, a 110-kDa protein
that belongs to the steroid receptor family, found in the
target cells cytosol and nucleus.
 The same receptor binds testosterone and DHT
 Before hormone binding, the receptor is inactive,
associated with HSP.
 When the hormone-receptor complex is formed, a
conformational change occurs, the HSP is released, the
receptor dimerizes and binds to a specific response
element in DNA, from which it regulates gene
expression.
 Question

 Describe mechanisms of action of testosterone

 Androgen Effects

 Androgens are responsible for the development of

male secondary sexual characteristics, maintain the
libido, and promote bone density.
 Androgens stimulate anabolism, particularly of
proteins. They are responsible for nitrogen retention,
muscle mass increase, lipid reduction, and sodium,
potassium, calcium, phosphate, and sulfate retention
 Androgens and bones

 Androgens also act on bone tissue, where the

response is dose dependent.
 Low doses, such as those circulating in blood before
puberty, induce epiphyseal cartilage proliferation
with increased synthesis of collagen and
glycosaminoglycans.
 High androgen concentrations stimulate calcium
uptake, promoting bone calcification and epiphyseal
closure.
 Androgens and hematocrit

 Androgens have stimulating effect on the synthesis

of erythropoietin, which explains the higher
hematocrit values that men have compared with
women.
 Mullerian-inhibiting substance.

 In fetal and prepubertal testes, Sertoli cells

Mullerian-inhibiting substance. This is a 150-kDa
protein that causes degeneration of Muller ducts.
 It is also secreted in very low amounts in adults,
acting in a paracrine manner directly on Leydig cells
with inhibitory effects on androgen synthesis
 Insulin-like 3 (Insl-3), member of the insulin like
peptides , is produced by Leydig cells after birth and
increases markedly during puberty.
 Adult mice with a mutation in the gene coding Insl-3
show lack of testes descent from the abdomen to the
scrotum (cryptorchidism) and spermatogenesis
alterations.
 Androgen Alterations

 Deficiency of 5α-reductase. The absence of 5α

reductase impairs the production of DHT. In males,
genitals are incompletely developed and the
individuals who suffer it appear as females at birth
(male incomplete hermaphroditism).
 Androgens insensitivity syndrome. This is a genetic
alteration linked to the X chromosome in which the
gene that controls testosterone and DHT synthesis is
affected. Androgen deficiency could be total or
partial; the phenotype is that of a female, presenting
as a pseudohermaphroditism syndrome.