THE ADRENAL GLAND

STEROIDOGENESIS AND

ITS CONTROL

DR SADIA HAROON

DEPT OPOPOPOPF BIOCHEMISTRY

SECOND YEAR MBBS

UGS MODULE Date 4.11.2021

STEROIDOGENESIS MCQ

Q1 .Steroid hormones are synthesised in all

of the following except

(A) Testes

(B) Ovaries

(C) Adrenal medulla

(D) Adrenal cortex

Q2. Steroid hormones are synthesised from

(A) Cholesterol

(B) 7-Dehydrocholesterol

(C) Calcitriol

(D) 7-Hydroxycholesterol

STEROIDOGENESIS MCQQ3 .A common intermediate in the synthesis

of all the steroid hormones is

(A) Pregnenolone

(B) 17-Hydroxypregnenolone

(C) Corticosterone

(D) Progesterone

Q4. A common intermediate in the synthesis

of cortisol and aldosterone is

A)Progesterone

(B) Testosterone

(C) Estradiol

(D) None of these

STEROIDOGENESIS MCQ

Q5A common intermediate in the synthesis

of estrogens is

(A) Cortisol

(B) Andostenedione

(C) Corticosterone

(D) 11-Deoxycorticosterone

Q6In adrenogenital syndrome due to total

absence of 21-hydroxylase in adrenal

cortex, there is

(A) Deficient secretion of glucocorticoids

(B) Deficient secretion of mineralcorticoids

(C) Excessive secretion of androgens

(D) All of these

Q7Androgens are synthesised in

(A) Leydig cells in testes

(B) Sertoli cells in testes

(C) Seminiferous tubules

(D) Prostate gland

Q8Testosterone is transported in blood by

(A) Transcortin

(B) Testosterone binding globulin

(C) Testosterone estrogen binding globulin

(D) Albumin

STEROIDOGENESIS MCQ

Q9 .The metabolites of androgens are

(A) 17-Hydroxysteroids

(B) 17-Ketosteroids

(C) 11-Hydroxysteroids

(D) 11-Ketosteroids

Q10. An androgen which is more powerful

than testosterone is

A)Androstenedione

(B) Dihydrotestosterone

(C) Androsterone

(D) Epiandrosterone

STEROIDOGENESIS MCQ

Q 11.Secretion of androgens is increased by

(A) LH

(B) FSH

(C) ACTH

(D) Growth hormone

Q12. During late pregnancy, the major source

of progesterone is

(A) Adrenal cortex (B) Placenta

(C) Corpus luteum (D) Graafian follicles

STEROIDOGENESIS MCQ

Q13. Progesterone is transported in blood by

(A) Transcortin

(B) Sex hormone binding globulin

(C) Albumin

(D) Testosterone estrogen binding globulin

Q 14 The major metabolite of progesterone is

(A) Pregnenolone

(B) Pregnanediol

(C) Estradiol

(D) Norethindrone

Q15. A hormone used for detection of pregnan-cy is

(A) Estrogen

(B) Progesterone

(C) Oxytocin

(D) Chorionic gonadotropin

Q16. Placenta secretes all of the following except

(A) FSH

(B) Progesterone

(C) Estrogen

(D) Chorionic gonadotropin

Q17.Women become susceptible to osteoporo-sis

after menopause due to decreased

(A) Secretion of Parathormone

(B) Conversion of vitamin D into calcitriol

(C) Secretion of estrogen

(D) Secretion of progesterone

Q18The major metabolite of progesterone is

(A) Pregnenolone

(B) Pregnanediol

(C) Estradiol

(D) Norethindrone

LEARNING OBJECTIVE

Introduction to male sex hormones or androgens

Functions of testicular cells

Synthesis and metabolism of testosterone

ADRENAL CORTEX

Is divided into 3 zones in the adult gland: Zona Glomerulosa, Zona Fasciculata, Zona Rericularis.

Is divided onto 4 zones in the fetal gland.

The three zones of the permanent cortex constitutes only 20% of the fetal gland’s size. The remaining zone (fetal cortex) comprises up to 80% of gland’s size during fetal life.

ADRENAL CORTEX: STEROID HORMONE

PRODUCTION

Aldosterone, sex hormones, cortisol

Synthesized from cholesterol–steroid ring

HORMONES OF ADRENAL CORTEX

Corticosteroids

Aldosterone (glomerulosa)

Mineralocorticoid

Cortisol (fasciculata)

Glucocorticoid

Sex hormones (reticularis)

Adrenal androgens

15

HORMONAL STIMULATION OF GLUCOCORTICOIDS

HPA AXIS (HYPOTHALAMIC/PITUITARY/ADRENAL AXIS)

With stress, hypothalamus sends CRH to anterior pituitary (adenohypophysis)

Pituitary secretes ACTH

ACTH goes to adrenal cortex where stimulates glucocorticoid secretion Sympathetic nervous system can also stimulate it

Adrenal cortex also secretes DHEA (dehydroepiandrosterone) Converted in peripheral tissues to testosterone and

estrogen (also steroid hormones)

Unclear function in relation to stress

Gonadotropic hormones

GnRH: pulsatile secretion

Cyclical secretion LH, FSH

Females: ovary

• LH: ovulation, corpus luteum

•FSH: dvpt follicle, oestradiol and progesterone

Males: testes

• LH: Leydig cells: testosterone

•FSH: Sertoli cells: spermatogenesis

FSH: inhibin: negative feedback

Gonadotropic hormones

SPERMATOGENESIS IN TESTIS

The development and maintenance of

spermatogenesis is dependent on

the pituitary gonadotropins; FSH, and

LH.

Both hormones are secreted and regulated

as a part of the HPG axis in response to

the hypothalamic gonadotropin-releasing

hormone (GnRH).

FSH stimulates the production of sperm.

INTERSTITIAL OR LEYDIG CELLS

Interstitial or Leydig cells are located in the

connective tissue surrounding the

seminiferous tubules.

They produce testosterone, the male sex

hormone responsible

for the growth and maintenance of the cells

of the germinal epithelium and

the development of secondary sex

characteristics.


They secrete testosterone, androstenedione

and dehydroepiandrosterone (DHEA), when

stimulated by the luteinizing hormone (LH)

which is released from the anterior pituitary in

response to gonadotrophin releasing hormone

which in turn is released by the hypothalamus.


The receptor allows the body to respond

appropriately to these hormones.

In males, chorionic gonadotropin stimulates

the development of cells in the testes called

Leydig cells, and luteinizing hormone

triggers these cells to produce androgens.

In the adult testis, estrogen is synthesized by

Leydig cells and the germ cells, producing a

relatively high concentration in rete testis fluid.

Estrogen receptors are present in the testis,

efferent ductules and epididymis of most species.


Leydig cells (LC) are present in the testicular

interstitial tissue, and their main function is to

produce testosterone (T) for the

maintenance of spermatogenesis and

extratesticular androgenic and anabolic

functions.


Testicular steroidogenesis initially involves

the production of T from cholesterol by the

interstitial Leydig cells of the testis. .

.. T undergoes conversion in the Leydig

cells, or in the prostate,

by 5α-reductase to 5α-dihydrotestosterone

(DHT), the most potent bioactive androgen.

Leydig cells stimulate the production of

sperm cells, and Sertoli cells nourish

developing sperm.

STEROIDOGENESIS

Steroidogenesis entails processes

by which cholesterol is converted

to biologically active steroid

hormones. ..

Qualitative regulation

determining the type of steroid to

be produced is mediated by many

enzymes and cofactors.

ADRENAL CORTEX: STEROID HORMONE

PRODUCTION

Figure 23-2: Synthesis pathways of steroid hormones

SYNTHESIS IN THE CORTEX

STEROID HORMONES: STRUCTURE

35

Steroid-secreting cells

have abundant smooth

ER

As opposed to rough ER in

protein-secreting cells

Steroids directly diffuse

across plasma

membrane

Not exocytosis

Abundant lipid droplets

Raw material from which

steroids made

In general:

TESTICULAR STEROIDOGENESIS

Testicular steroidogenesis is a

fine-regulated process, and its

main product, testosterone (T),

has a crucial role in fetal

development and maturation

and in adulthood for the

maintenance of secondary sexual

function and spermatogenesis


The primary site for the synthesis of

testosterone within the mammalian

testis is the interstitial cells of

Leydig, which are specialized cells

located in the angular spaces

between seminiferous tubules


When puberty begins,

usually between the ages of 9 and 15,

the pituitary gland — located near

the brain —

secretes hormones that stimulate the

testicles to produce testosterone.

The production of testosterone

brings about many physical changes.

EFFECT OF AGING .

Although the mitochondrial and smooth

endoplasmic reticulum steroidogenic enzymes are

reduced in aging Leydig cells, their levels

nonetheless are sufficient to support high levels

of steroid production if enough cholesterol is

translocated into the mitochondria and thus is

available to CYP11A1 of the inner .

ROLE OF GONADOTROPHINS

The hypothalamus produces

gonadotropin-releasing hormone,

which signals the pituitary gland to

make follicle-stimulating hormone (

FSH ) and luteinizing hormone (

LH ).

Luteinizing hormone then signals

the testes to produce testosterone.

LOW LEVELS OF TESTICULAR STEROIDS

Injury (trauma, interrupted blood supply to

the testes) or infection of the testes

(orchitis)

Chemotherapy for cancer.

Metabolic disorders such as

hemochromatosis (too much iron in the

body)

Dysfunction or tumors of the pituitary

gland

STEROID HORMONES SYNTHESIS

Steroids are derivatives of cholesterol

Cholesterol is from the lipid droplets in

cortical cells (cholesterol esters in

LDL)

Removed cholesterol is replenished by

cholesterol in LDL in blood or synthesized

from acetate

Steroid hormones are synthesized and secreted on

demand (not stored)

The first and rate-limiting step in the synthesis of all

steroid hormones is conversion of cholesterol to

pregnenolone by the enzyme cholesterol dismolase (aka

cholesterol side chain cleavage (SCC) enzyme

Newly synthesized steroid hormones are rapidly secreted

from the cell

Following secretion, all steroids bind to some extent to

plasma proteins: CBG and albumin

STEROID HORMONES SYNTHESIS (CONT.)

ENZYMES IN STEROID BIOSYNTHESIS

Side-chain cleavage enzyme; desmolase

(P450scc)

3 β-hydroxysteroid dehydrogenase (3 β HSD)

17 α-hydroxylase/17,20 lyase (P450 c17):

Adrenarche

* not present in glumerulosa cells

21-hydroxylase (P450c21)

11 beta-hydroxylase (P450c11)

Aldosterone synthase

GENETIC DEFECTS IN ADRENAL STEROIDOGENESIS

Congenital adrenal hyperplasia

ACTH ِ Adrenal hyperplasia

• 21-hydroxylase (P450c21) deficiency:

cortisol, corticosterone, and aldosterone deficiency

*ACTH Adrenal hypertrophy and high amounts of androgen

* Virilization of female (masculanization)

cortisol

STEROID HORMONES: ACTION

ANDROGENS

are hormones that contribute to growth and

reproduction in both men and women.

Androgens are usually thought of as male

hormones, but the female body naturally

produces a small amount of androgens too.

Androgen deficiency in women is a controversial

concept.

CORTISOL: ROLE IN DISEASES AND

MEDICATION

Use as immunosuppressant

Hyperimmune reactions (bee stings)

Serious side effects

Hypercortisolism (Cushing's syndrome)

Tumors (pituitary or adrenal)

Iatrogenic (physician caused)

Hypocortisolism (Addison's disease)

THE ADRENAL GLAND

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