Testosterone: A Comprehensive Physiology Review for Medical Students
1. Introduction
Testosterone is the principal androgenic steroid hormone in humans, playing a central
role in male sexual differentiation, reproductive function, anabolic
processes, and overall metabolic regulation. Although predominantly
associated with males, it is also present and physiologically important in
females.
It belongs to the class of C19 steroid hormones derived from
cholesterol and is synthesized primarily in the testes, with smaller
contributions from adrenal glands and ovaries.
2. Chemistry and Structure
Testosterone is a lipophilic steroid hormone synthesized from
cholesterol via a series of enzymatic reactions:
- Molecular
formula: C₁₉H₂₈O₂
- Structure:
Four-ring steroid nucleus (cyclopentanoperhydrophenanthrene)
- Functional
groups:
- Ketone group
at C3
- Hydroxyl group
at C17
Key Derivatives
- Dihydrotestosterone
(DHT): More potent androgen (via 5α-reductase)
- Estradiol (E2): Formed via aromatization
(important in bone and brain)
3. Sites of Synthesis
In Males
- Leydig cells of testes (major source, ~95%)
In Females
- Ovarian theca cells
- Adrenal cortex (zona reticularis)
4. Biosynthesis of Testosterone
Testosterone synthesis occurs via the steroidogenic pathway:
Cholesterol → Pregnenolone → Progesterone → 17α-hydroxyprogesterone →
Androstenedione → Testosterone
Key Enzymes
- Cholesterol
desmolase (CYP11A1)
- 17α-hydroxylase
(CYP17A1)
- 17β-hydroxysteroid
dehydrogenase
Regulation by LH
The process is stimulated by Luteinizing Hormone (LH) from the
anterior pituitary.
5. Regulation:
Hypothalamic–Pituitary–Gonadal (HPG) Axis
Testosterone secretion is tightly regulated by the HPG axis:
- Hypothalamus →
releases GnRH
- Pituitary →
secretes:
- LH → stimulates Leydig cells → testosterone production
- FSH → acts on Sertoli cells (spermatogenesis)
Negative Feedback
Testosterone inhibits:
- GnRH secretion
- LH secretion
6. Transport in Blood
Testosterone circulates in three forms:
- Bound to SHBG (Sex Hormone
Binding Globulin) (~60%) → biologically inactive
- Bound to albumin (~38%) → weakly bound,
bioavailable
- Free testosterone (~2%) → biologically active
7. Mechanism of Action
Testosterone acts via intracellular androgen receptors (ARs):
- Diffuses
through cell membrane
- Binds to
androgen receptor in cytoplasm
- Hormone-receptor
complex translocates to nucleus
- Binds to DNA
(androgen response elements)
- Modulates gene
transcription
DHT Action
- Higher affinity
for androgen receptor
- Responsible for
many androgenic effects (e.g., prostate growth, hair pattern)
8. Physiological Actions
A. Fetal Life
- Development of male
internal genitalia (via testosterone)
- Development of external
genitalia (via DHT)
B. Puberty
- Enlargement of
testes and penis
- Development of
secondary sexual characteristics:
- Facial,
axillary, pubic hair
- Deepening of
voice (laryngeal enlargement)
- Increased
libido
C. Adult Male Functions
1. Reproductive System
- Maintenance of
spermatogenesis (with FSH)
- Growth and
function of accessory glands (prostate, seminal vesicles)
2. Anabolic Effects
- Increased
protein synthesis
- Muscle mass and
strength
- Bone growth and
density
3. Hematopoietic Effects
- Stimulates
erythropoiesis → ↑ hemoglobin
4. Metabolic Effects
- Mild increase
in basal metabolic rate
- Fat
distribution (central vs peripheral)
5. CNS Effects
- Libido
- Aggression and
mood modulation
D. Functions in Females
- Contributes to
libido
- Precursor for
estrogen synthesis
- Role in bone
health and muscle mass
9. Role of Dihydrotestosterone (DHT)
DHT is formed by 5α-reductase in target tissues:
Key Actions
- Development of
prostate
- Male pattern
baldness
- Sebaceous gland
activity
- External
genital differentiation
10. Circadian Rhythm
- Testosterone
levels exhibit diurnal variation
- Peak: Early
morning (6–8 AM)
- Decline with
age (andropause)
11. Life Span Changes
Fetal Life
- High levels →
sexual differentiation
Childhood
- Low levels
Puberty
- Sharp increase
Aging
- Gradual decline
(~1% per year after 30)
12. Clinical Correlations
A. Hypogonadism
Causes:
- Primary
(testicular failure)
- Secondary
(pituitary/hypothalamic)
Features:
- Delayed puberty
- Infertility
- Decreased
muscle mass
- Erectile
dysfunction
B. Hyperandrogenism
- Excess
testosterone (e.g., tumors, anabolic steroids)
- Features:
- Acne
- Aggression
- Infertility
C. Androgen Insensitivity Syndrome
- Defective
androgen receptors
- XY individuals
with female phenotype
D. Benign Prostatic Hyperplasia (BPH)
- Mediated by DHT
- Enlarged
prostate → urinary symptoms
E. Male Pattern Baldness
- DHT-dependent
hair follicle miniaturization
F. Polycystic Ovary Syndrome (PCOS)
- Elevated
androgens in females
- Symptoms:
- Hirsutism
- Acne
- Menstrual
irregularities
13. Pharmacology (Brief Overview)
Therapeutic Uses
- Testosterone
replacement therapy
- Delayed puberty
- Gender-affirming
therapy
Anti-androgens
- Finasteride
(5α-reductase inhibitor)
- Flutamide
(androgen receptor blocker)
14. Laboratory Assessment
- Total
testosterone
- Free
testosterone
- SHBG levels
Normal Range (Adult Male)
- ~300–1000 ng/dL
15. Summary (Exam-Oriented Points)
- Testosterone is
the primary male androgen produced by Leydig cells.
- Regulated via HPG
axis (GnRH → LH → Testosterone).
- Circulates
mostly bound to SHBG.
- Acts via nuclear
androgen receptors.
- Converted to:
- DHT (more potent androgen)
- Estradiol (important for bone)
- Responsible
for:
- Sexual
differentiation
- Secondary
sexual characteristics
- Anabolic and
metabolic effects
- Clinical
relevance includes:
- Hypogonadism
- PCOS
- BPH
- Androgen
insensitivity
16. Quick Revision Table
|
Feature |
Testosterone |
|
Type |
Steroid hormone |
|
Source |
Leydig cells |
|
Regulation |
LH (HPG axis) |
|
Transport |
SHBG-bound |
|
Active form |
Free testosterone, DHT |
|
Mechanism |
Nuclear receptor |
|
Functions |
Reproductive, anabolic, metabolic |
17. Conclusion
Testosterone is a multifunctional hormone essential for male
physiology and significant in female health. Its precise regulation,
conversion to active metabolites, and systemic effects make it a
cornerstone topic in medical physiology and clinical medicine.