Androgen Biosynthesis Functions Testosterone Cholesterol Testosterone Cholesterol Testosterone

Androgen Biosynthesis & Functions

Testosterone

Cholesterol Testosterone

Cholesterol Testosterone Dihydrotestosterone (DHT)

Cholesterol Dehydroepiandrosterone Androstenedione Testosterone Dihydrotestosterone (DHT)

Cholesterol Dehydroepiandrosterone Progesterone Androstenedione Estrone Testosterone Estradiol Dihydrotestosterone (DHT)

Cholesterol Dehydroepiandrosterone Progesterone Aldosterone Cortisol Androstenedione Estrone Testosterone Estradiol Dihydrotestosterone (DHT)

Cholesterol Pregnanolone 17 -OH P. Dehydroepiandrosterone Progesterone 17 -OH P. Androstenedione Estrone Aldosterone Cortisol Testosterone Estradiol Dihydrotestosterone (DHT)

Cholesterol (1) Pregnanolone (2) Progesterone (4) Aldosterone (3) 17 -OH P. (2) (3) 17 -OH P. (4) Cortisol (3) (6) 5 α reductase Dehydroepiandrosterone (2) Androstenedione (5) Testosterone (6) Dihydrotestosterone (DHT) Estrone (5) Estradiol

Cholesterol (1) Pregnanolone (2) Progesterone (4) Aldosterone (3) 17 -OH P. (2) (3) 17 -OH P. (4) Cortisol (3) Dehydroepiandrosterone (2) Androstenedione (5) Testosterone (6) Dihydrotestosterone (DHT) Estrone (5) Estradiol

Cholesterol (4) 21 hydroxylase (1) Pregnanolone (2) Progesterone (4) Aldosterone (3) 17 -OH P. (2) (3) 17 -OH P. (4) Cortisol (3) (6) 5 α reductase Dehydroepiandrosterone (2) Androstenedione (5) Testosterone (6) Dihydrotestosterone (DHT) Estrone (5) Estradiol

(1) STAR (2) 3 β HS dehydrogenase (3) 17 α hydroxylase (4) 21 hydroxylase (5) 17 β HS dehydrogenase (6) 5 α reductase Cholesterol (1) Pregnanolone (2) Progesterone (4) Aldosterone (3) 17 -OH P. (2) (3) 17 -OH P. (4) Cortisol (3) Dehydroepiandrosterone (2) Androstenedione (5) Testosterone (6) Dihydrotestosterone (DHT) Estrone (5) Estradiol

Cholesterol (4) 21 hydroxylase (1) Pregnanolone (2) Progesterone (4) Aldosterone (3) 17 -OH P. (2) (3) 17 -OH P. (4) Cortisol (3) (6) 5 α reductase Dehydroepiandrosterone (2) Androstenedione (5) Testosterone (6) Dihydrotestosterone (DHT) Estrone (5) Estradiol

Enzymatic Defects § 21 hydroxylase deficiency: Most common cause of “Congenital Adrenal Hyperplasia” § STAR mutation: Severe adrenal failure & Male Karyotype shows female external genitalia § 3 β HS dehydrogenase deficiency: Adrenal failure. Male shows disturbance in virilization & Female shows virilizarion of external genitalia

Enzymatic Defects § 17 α hydroxylase mutation: Decreases Cortisol but normal Aldosterone & Hypogonadism § 17 β HS dehydrogenase mutation: Disturbed virilization of male external genitalia. Hirsutism and clitoromegaly in the female § 5 α reductase deficiency: Pseudo-vaginal perineo-scrotal hypospadius

Androgens Serum Level Potency (Androgenicity) 500 ng/dl 15 % 150 ng/dl 39 % Testosterone Testis (95 %) 610 ng/dl 100 % DHT Peripheral Conversion 55 ng/dl 181 % Source DHEAS Androstenedione Adrenal Cortex

Androgen Transport Testosterone Bound to SHBG (40 %) Bound to Albumen (58 %) Free (2 %)

Androgen Transport Testosterone Bound to SHBG (40 %) Bound to Albumen (58 %) Bioavailable Testosterone Free (2 %)

Testosterone § Bioavailable testosterone is ready for action & metabolism § Testosterone acts as an endocrine, paracrine & autocrine factor § Its receptors are found on Sertoli cell nucleus, Leydig cell & peri-tubular cells § Serum concentration of DHT is about 1/10 that of testosterone

5 α reductase Type I • • • Skin Liver Brain Type II • • • Testis Prostate SV

Sex Hormone Binding Globulin (SHBG) • Aging • Liver Cirrhosis • Estrogen Therapy • Tamoxifen • Hyperthyroidism • Antiepileptics

Sex Hormone Binding Globulin (SHBG) • Aging • Liver Cirrhosis • Estrogen Therapy • Tamoxifen • Hyperthyroidism • Antiepileptics • Obesity • Androgen Therapy • Hypothyroidism • Hyperprolactinemia • Acromegaly

Sex Hormone Binding Globulin (SHBG) • Aging • Liver Cirrhosis • Estrogen Therapy • Tamoxifen • Hyperthyroidism • Antiepileptics SHBG • Obesity • Androgen Therapy • Hypothyroidism • Hyperprolactinemia • Acromegaly Free & Bioavailable T.

Androgen Metabolism Hepatic (50%) Urine Extra-hepatic (50%) (e. g. skin, fatty tissue, brain) DHT Estradiol

Functions of Androgens �Androgenic Actions �Anabolic Actions

Functions of Androgens �Androgenic Actions

Functions of Androgens �Androgenic Actions ü Fetal Sex Differentiation

XX XY Primitive Gonad SRY Testis MIF Leydig Cell Sertoli C. Disappearance 5 α reductase Ovary Female Phenotype Testosterone DHT Int. Genitalia § Epididymis § VD § SV § ED Ext. Genitalia § Penis § Scrotum § Prostate § BU Gland

Glans Area Epithelial Tag Urogenital Fold Urogenital Groove Lateral Part of the Tubercle Anal Pit Genital Tubercle

Glans Area Epithelial Tag Urogenital Fold Urogenital Groove Genital Tubercle Lateral Part of the Tubercle Anal Pit Glans Epithelial Tag Coronal Sulcus 10 th Week Urethral Fold Urogenital Groove Lateral Tubercle (Corpus) Labio-scrptal Swelling Urethral Raphé Anal Tubercle Anus

Body of Clitoris External urethral Orifice Prepuce Glans Penis Glans Prepuce External urethral Orifice Shaft of the Penis Labium Minora Labium Majora Raphe of Penis Perineal Raphé Scrotum Vaginal orifice Anus Male Posterior Commisure Female

Development of External Genitalia Female Male Genital Tubercle Clitoris (Glans & Corpora) Penis (Glans, Corpora cavernosa & Corpus spongiosum) Urogenital Folds § Labia minora § Perineal raphé § Perianal tissue & Ext. anal sphincter § Ventral aspect of penis § Most of penile urethra § Perineal raphé § Perianal tissue & Ext. anal sphincter Labio-scrotal Folds Labia majora Scrotum

Functions of Androgens �Androgenic Actions ü Fetal Sex Differentiation ü Sex Organs Growth (Penis, scrotum, prostate & SV)

Functions of Androgens �Androgenic Actions ü Fetal Sex Differentiation ü Sex Organs Growth ü 2 ry Sex Characters

2 ry Sex Characters § Hair distribution § Sebaceous & Apocrine gland secretion § Larynx & vocal cords § Linear growth & closure of epiphysis of long bones § Behavioral changes § Sexual desire (libido)

Span Height Body Measurements

Span Head-Symphysis Height Symphysis-Foot Body Measurements

Functions of Androgens �Androgenic Actions ü Fetal Sex Differentiation ü Sex Organs Growth ü 2 ry Sex Characters ü Reproduction

Functions of Androgens �Anabolic Actions

Functions of Androgens �Anabolic Actions ü Protein Synthesis

Functions of Androgens �Anabolic Actions ü Protein Synthesis ü Increase Erythropoeitin

Functions of Androgens �Anabolic Actions ü Protein Synthesis ü Increase Erythropoeitin ü Increase LDL & Decrease HDL

When to Measure …. . ? ? ? � Free Testosterone …… (If alteration of SHBG is suspected)

When to Measure …. . ? ? ? � Free Testosterone …… � Estradiol ……… § Estrogen secreting tumor § Gynecomastia with obesity § ? ? Androgen insensitivity syndrome (AIS)

When to Measure …. . ? ? ? � Free Testosterone …… � Estradiol ……… � DHT ……. . (To diagnose 5 α reductase deficiency)

When to Measure …. . ? ? ? � Free Testosterone …… � Estradiol ……… � DHT ……. . � Inhibin-B ……. § Direct relation with spermatogenesis & sperm cont (Inhibin-B / FSH ratio) § Diagnosis of bilateral Anorchia

Capsule Summary § Testosterone & DHT are the main androgens § 21 hydroxylase deficiency is the main cause of Congenital Adrenal Hyperplasia § Testosterone starts to function during intrauterine period § Testosterone has Androgenic & Anabolic functions § Germ cells have no hormonal receptors

Thank You

(1) Steroidogenic Acute Regulatory protein (2) 3 β Hydroxysteroid dehydrogenase (3) 17 α hydroxylase (4) 21 hydroxylase (5) 17 β Hydroxysteroid dehydrogenase (6) 5 α reductase Cholesterol (1) Pregnanolone (2) Progesterone (4) Aldosterone (3) (3) 17 -OH P. (2) 17 -OH P. (4) Cortisol (3) Dehydroepiandrosterone (2) Androstenedione (5) Testosterone (6) Dihydrotestosterone (DHT) Estrone (5) Estradiol

XX XY Primitive Gonad SRY Testis MIF Leydig Cell Sertoli C. Disappearance 5 α reductase Ovary Female Phenotype Testosterone DHT Int. Genitalia § Epididymis § VD § SV § ED Ext. Genitalia § Penis § Scrotum § Prostate § BU Gland

Hypothalamus Estrogen (- ve) Gn. RH “Aromatization” Only LH Only FSH Ant. 1 Pit. LH FSH “Inhibin B” (- ve) “Activin” (+ ve) Testis Sertoli Leydig Cell Sem. Tub. Cells Testosterone Sperm

(1) STAR (2) 3 β HS dehydrogenase (3) 17 α hydroxylase (4) 21 hydroxylase (5) 17 β HS dehydrogenase (6) 5 α reductase Cholesterol (1) Pregnanolone (2) Progesterone (4) Deoxicorticosterone (3) 17 -OH P. (2) 17 -OH P. (3) (4) Dehydroepiandrosterone (2) Androstenedione (5) 11 -deoxicortisol Corticosterone Aldosterone (3) Testosterone (6) Cortisol Dihydrotestosterone (DHT) Estrone (5) Estradiol

+ External urethral Orifice Body of Clitoris Prepuce Glans Penis Glans Prepuce External urethral Orifice Shaft of the Penis Labium Mins Labium Majs Raphe of Penis Perineal Raphe Scrotum Ans Vaginal orifice Posterior Commisre