Hormones of The Gonads

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

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Hormones of the Gonads

MBBS 300 LEVEL

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

Figure 2. Biosynthesis of Estrogens in the ovary

Figure 3. Steroid hormone biosynthesis pathways in the ovary

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