Hormones of the Gonads

MBBS 300 LEVEL

 Learning Objectives
• To understand the enzyme system in gonads
• To understand the hormones produced by
male and female gonads
• To highlight the regulatory mechanisms of
hormones of the gonads
• To identify the functions of each hormones
• Clinical implications
 INTRODUCTION
The female ovaries and the male testicles,
responsible for many sex characteristics, are
referred to as the gonad glands or sex organs
 Female ovaries synthesize the hormones estrogen
and progesterone in varying amounts depending
on where in her cycle a woman is
 Testicular production of the sex hormone
testosterone (a principle androgen) begins during
fetal development, continues for a short time
after birth, nearly ceases during childhood, and
then resumes at puberty
• MALE SEX HORMONE
Testicular Androgens:
• Substrate is derived as circulating cholesterol
• The conversion of pregnenolone to testosterone requires the action of
5 enzymes , all found in the endoplasmic reticulum ER of the testes cells
• The conversion of pregnenolone to testosterone is referred to as the
"Progesterone Pathway“
• Leydig cells, also known as interstitial cells of Leydig,found adjacent to
the seminiferous tubules in the testicle
• Enzymes are:
(1) 17α-Hydroxylase
(2) C17,20 Lyase
(3) 3β-Hydroxysteroid Dehydrogenase (3β-OHSD)
(4) D5-D4-Isomerase
(5) 17 β -Hydroxysteroid Dehydrogenase (17 β -OHSD)
Androgen production
• Leydig cells releases a class of hormones called
androgens(19-carbon steroids
• They secrete:
1.testosterone,
2. androstenedione and
3. dehydroepiandrosterone) when stimulated by luteinizing
hormone(LH), released from anterior pituitary in response to
gonadotrophin releasinghormone from hypothalamus
• LH –receptor complex activation
• Receptor is a G-protein coupled receptor
• LH in males is called interstitial cell stimulating
hormone(ICSH)
 ACTIONS AND FUNCTIONS OF MALE
TESTICULAR HORMONE

Circulation

Figure 1. Male sex hormones produced by Leydig cells of testes

• Dihydrotestosterone (DHT), is the most potent
androgen, it is formed from testosterone, by
the reduction of the A ring through the action
of the enzyme 5α-Reductase.
• The testes also produce 17 β -estradiol, the
female sex hormone in small amounts, but
most of the estrogens produced by the male
are derived from peripheral aromatization of
testosterone
 FUNCTIONS OF MALE ANDROGEN
• The androgens, principally testosterone and DHT, acting through nuclear receptors
are involved in:
(1) sexual differentiation
(2) spermatogenesis
(3) development of sexual organs
(4) anabolic metabolism and gene regulation
(5) male pattern behavior
• During the initial stages of gestation, the development of male and female
embryos is indistinguishable.
• At about day 56, hormones become involved.
• All embryos spontaneously develop into phenotypic females in the absence of a Y-
chromosome induced event.
• A male specific gene has been detected in mice which is associated with
differentiation of the primitive gonad, and lies within the sex determining region
(sry) of the Y chromosome.
• When the sry gene is injected into XX female embryos, normal male mice develop
• FEMALE SEX HORMONES
 estrogens
progesterone
 Ovarian Sex Steroid Hormones:

Biosynthesis of Estrogens:
• The ovaries are bifunctional organs that
produce both estrogens and progestagens.
• The most active naturally occurring hormones
of these groups are 17β-estradiol (E2) and
progesterone
• Biosynthetic Pathways of Steroid hormones in the Ovary
• The endogenous steroid hormone synthesis in the ovary occurs
via one of two pathways: the (delta)5 (3β (beta)-hydroxysteroid
HSD)-pathway or the (delta)4 - (3 ketone-pathway).
• The ovary, like the adrenal gland, produces all three classes of
steroid hormones from cholesterol
• The ovarian steroid hormones are synthesized in both interstitial
and follicular cells.
1. The pathway involve (delta)4 converts pregnenolone to
progesterone and is the main pathway in the corpus luteum.
2. Another pathway,(delta)5-pathway converts pregnenolone to
androgens and, subsequently, estrogens, and is the preferred
pathway in the thecal cells (Figures 2 & 3).
 Synthesis of progesterone in the Ovary
In mammals, progesterone is synthesized from pregnenolone, with
cholesterol as a precursor.
• Cholesterol undergoes double oxidation to produce 20, 22-
dihydroxycholesterol.
• This vicinal diol is further oxidized with loss of the side chain starting at
position C-22 to produce pregnenolone;
• this reaction is catalyzed by cytochrome P450scc
The conversion of pregnenolone to progesterone takes place in two steps.
• First, the 3-hydroxyl group is oxidized to a keto group and
• second, the double bond is moved from C-5 to C-4 through a keto/enol
tautomerization reaction
• This reaction is catalyzed by 3β-hydrosteroid dehydrogenase and
5,4isomerases
 Ovarian hormones

Figure 2. Biosynthesis of Estrogens in the ovary

 FSH

GRANULOSA CELL

Figure 3. Steroid hormone biosynthesis pathways in the ovary

(Gupta et al., 2007)
• Progesterone is part of the group of C 21 steroids, which also
includes pregnenolone and 17OH-progesterone. Progesterone is
accountable for all the progestational effects, whereas pregnenolone
is the precursor for all steroid hormones.
• 17OH-progesterone has little biologic activity.
• Progesterone and 17OH-progesterone are primarily synthesized by
the corpus luteum in the luteal phase of the menstrual cycle and by
the placenta if pregnancy occurs.
• The levels of progesterone at concentrations greater than 4–5 ng/mL
(12.7– 15.9 nmol/L) are suggestive of ovulation
• Enzymes involved in the hepatic metabolism of progesterone include
principally, CYP2C19, CYP3A4 and CYP2C9
• Progesterone is rapidly metabolized by the liver and has a half-life of
approximately 5 min.
• It is converted to pregnanediol and conjugated to glucuronic acid in
the liver.
• Pregnanediol glucuronide is excreted in the urine
 Assignments
• What are gonads?
• Identify the hormones of the gonads
• Concisely describe the biosynthesis of female
sex hormones
• Describe the mechanism of action and
biochemical functions of testosterone in males