Case 4 - Male Puberty

GnRH - released by the hypothalamus to stimulate FSH and LH secretion from the anterior pituitary


FSH - released by anterior pituitary, stimulates sertoli cells to promote spermatogenesis


LH- released by anterior pituitary, stimulates cholesterol desmolase in leydig cells, end result is that it stimulates the production of testosterone


Testosterone :
-paracrine effects - diffuses into sertoli cells to also promote spermatgenesis
-endocrine effects - leads to male secondary sexual characteristics
-negatively feedback on GnRH and LH secretion


Inhibin - secreted by sertoli cells, negatively feedback on FSH secretion

Pulsatile GnRH secretions from the hypothalamus stimulate secretion of FSH and LH from pituitary gland Pulsatile gonadotropin secretions from the anterior pituitary LH acts on parallel cells (theca cells and leydig cells) FSH acts on parallel cells (sertoli cells and granulosa cells)

Negative feedback loops: -Inhibin B on pituitary -Sex hormone (testosterone, progesterone, estradiol) on pituitary and hypothalamus -Adjusted by altering frequency of pulsatile secretions

Range of onset of puberty - 9 to 14, puberty is completed in 2 to 4.5 years
First sign of puberty - enlargement of testes to >2.5 cm, results from growth of seminiferous tubules and Leydig cells
Pubertal spurt occurs at stages 3-4 - result of increased secretion of growth hormone and secretion of testosterone
Voice deepening - vocal cords increase in length by 50%, larynx, cricothyroid cartilage, and laryngeal muscles increase in size - Adam’s apple
Secondary sex characteristics - not essential for production and movement of gametes
Men have 150% muscle mass of women, women have 200% body fat of men
Androgenic effects vs. anabolic effects - growth of male reproductive system and development of secondary sex characteristics vs. growth in somatic tissue
Mandible and nose enlarge more in boys

The sexual differentiation of genetic males begins at the end of the 6th week, controlled by SRY gene.


The SRY protein controls somatic support cell development into pre-Sertoli cells.


Mesonephric mesenchymal cells recruited into the gonadal ridge - give rise to Leydig cells, myoepithelial cells, interstitial cells, and endothelial cells.


Differentiating Sertoli cells, germ cells and myoepithelial cells organize into testis cords (future seminiferous tubules).


The deepest portions of the somatic support cells differentiate into the rete testis - connects with mesonephric tubules at puberty to connect the seminiferous tubules to the mesonephric duct - become efferent ductules of the testes, and vasa deferentia.


The müllerian ducts degenerate, distal vas deferens sprouts the seminal vesicle, and prostate and bulbourethral glands grow from the adjacent pelvic urethra.


Simultaneously, the indifferent external genitalia (consisting of paired urogenital and labioscrotal folds on either side of the urogenital plate and an anterior genital tubercle) differentiate into the penis and scrotum. Late in fetal development, the testes descend into the scrotum through the inguinal canals.

The testes are composed of seminiferous tubules and the interstitial cells of Leydig, which produce testosterone.

The seminiferous tubules are lined by seminiferous epithelium, and are the site of spermatogenesis.

Sertoli cells span from the basal lamina to the lumen, are connected by tight junctions and surround the developing germ cells.

Leydig cells need cholesterol in order to synthesize androgens - can create de novo from acetyl coenzyme A or uptake LDL through receptor-mediated endocytosis. Preferred pathway: Cholesterol -(side chain cleavage enzyme)-> Pregnenolone -(17α-hydroxylase)-> 17α-hydroxypregnenolone -(17,20 desmolase)-> Dehydroepiandrosterone (DHEA) -(17beta-hydroxysteroid dehydrogenase)-> Androstenediol -(3beta-hydroxysteroid dehydrogenase)-> Testosterone Step 1: side chain cleaved, occurs in mitochondria, rate-limiting step for pathway - since LH stimulates this step, LH controls rate of production - stimulates conversion by increasing affinity of enzyme for cholesterol, and increasing production of enzyme (SCC - side chain cleavage) Step 2: hydroxyl group added, occurs in smooth endoplasmic reticulum (SER) Step 3: side chain removed, occurs in SER, same enzyme as step 2 but different activity Step 4: ketone to hydroxyl group, SER Step 5: hydroxyl group oxidized to ketone Target tissues: • Differentiation of epididymis, vas/ductus deferens, seminal vesicles • Growth spurt during puberty Penis, seminal vesicles, sperm (from proliferation/growth of seminiferous tubules), muscle, RBCs • Deepening of voice (vocal cords) • Closure of epiphyseal plates (it’s actually estrogen aromatized from testosterone that does this) • Increase in libido • Anterior pituitary, hypothalamus - negative feedback

Spermatogenesis - seminiferous tubules of the testes, diploid spermatogonium divides mitotically to produce two primary spermatocytes.


These each undergo meiosis 1 to produce haploid secondary spermatocytes. The secondary spermatocytes enter meiosis 2 and divide into spermatids. They attach to Sertoli cells and undergo: cytoplasm reorganization, nuclear changes, acrosome formation, and flagella formation. Spermiation - spermatozoa released from Sertoli cells, become motile in the epididymis.
Sertoli cells are around the tubules and they protect the sperm precursor cells by providing structural and metabolic support. FSH stimulates the production of androgen binding protein which maintains high levels of testosterone needed to initiated spermatogenesis.

Androgen insensitivity syndrome - caused by mutations in the androgen receptor gene, located on the X chromosome - X-linked recessive, androgen receptor mediated Wolffian duct development does not occur. However, antimüllerian hormone activity is present and the individual does not have müllerian development. The vagina is short and it ends blindly. The uterus and fallopian tubes are absent and the testes are normally developed, but abnormally positioned. 5-alpha-reductase deficiency - caused by an autosomal recessive gene mutation in the 5 -ARD type 2 gene, 5-ARD enzyme is responsible for conversion of testosterone to dihydrotestosterone. Genetic males have female-appearing external genitalia due to an absence of dihydrotestosterone effect, have normal internal genitalia and normal wolffian structures but are undervirilized and display ambiguous external genitalia, may have hypospadias or a micropenis - fertility is maintained SRY mutations - since there is no gonad or antimüllerian hormone, the internal (and external) genitalia is female, with streak gonads present. The external genitals may vary between normal female and normal male, with the majority female. When SRY is mutated, no secondary sexual (male or female) characteristics develop at puberty, and menstruation does not occur due to lack of estrogen - no growth spurt and pubic hair develops scantly. Klinefelters syndrome - 47,XXY, very small testes, often some degree of androgen insensitivity, gynecomastia, infertility