10/12- Disease of Male Reproduction Flashcards
What is seen here?
- Red arrow
- Yellow arrow
- Blue arrow
- Green arrow
- Red arrow: Leydig cells
- Yellow arrow: Basement membrane
- Blue arrow: Sertoli cells
- Green arrow: Germ cells
From outside to insider, germ cells:
- Spermatogonia
- Spermatocytes
- Spermatids
- Spermatozoa
What are Sertoli cells?
- Function
- Hormones produced
Function:
- Provide structural support
- Produce important hormones:
- Anti-Mullerian hormone (AMH)
- Inhibin and Activin: secreted after puberty; work together to regulate FSH secretion
- Estradiol: aromatase from SCs converts testosterone to estradiol to direct spermatogenesis
How do levels of plasma testosterone change over life?
- Starts ~ 8 wks of gestation
- During fetal life, levels increase to near adult male levels (directing male sexual organ development)
- Drop at birth
- Rise throughout puberty
- Peaks in early adulthood
T/F: Aging is associated with decreased T in healthy males
False
Describe steroidogenesis?
- Cholesterol = initial substrate
- Binds LDL cholesterol receptor or produced endogenously
- StAR
- Pregnenolone
Done in the fetal Leydig cell
What are typical testicular steroid secretion rates?
- Testosterone: 7 mg/day
- DHT: 560 ug/d (+ some peripheral conversion)
- E2: 21 ug/d (+30 ug/d from peripheral conversion of testosterone)
Describe the different types/forms of testosterone in regards to total levels?
Which form(s) is/are bioavailable?
- SHBG bound (54%)
- Albumin bound (44%)
- Free (2%)
Bioavailable:
- Free
- Albumin bound
These 2 forms bind the AR receptor in the target tissue
What are effects of T/DHT-AR on the human body?
- Stimulation of erythropoiesis
- Enlargement of larynx, thickening of vocal cords
- Bone: BMD, peak bone mass, long bone growth
- Body composition, strength, muscle mass
- Hair growth and devo of mail hair distribution
- Genital appearance and spermatogenesis
- Cognitive function, mood, sexual function
What are some Androgen Insensitivity Syndromes?
Symptoms
Complete androgen insensitivity
- Female external phenotype
- Lack axillary and pubic hair (androgen receptor dependent)
- Retained testes
- Blind ending vagina
- No uterus
Incomplete androgen insensitivity
- Phenotype varies from infertility to gynecomastia and various degrees of hypospadias
Minimal androgen insensitivity
_____ is essential for the development of the male sexual phenotype during embryologic development
AR (androgen receptor) signaling is essential for the development of the male sexual phenotype during embryologic development
What is seen in SRD5-2 deficiency?
At birth:
- Lack of phallus
- Bifid scrotum
- External female genitalia
At puberty:
- Develop phallus
- Phenotype becomes male in adulthood
Why do SRD5-2 deficient people have female phenotype at birth?
How do they undergo near normal puberty?
- DHT is essential for virilization of external genitalia (and the prostate)
- Pubescent changes depend on testosterone, not DHT
What are abnormalities of the adult phenotype in SRD5-2 deficient individuals?
- Lack of male pattern baldness
- Lack of body hair (facial and pubic hair present
- Small prostate
What happens when there is a lack of testosterone production during the 2nd half of fetal devo and 1st year of life?
Testosterone at this stage is responsible for growth of penis and descent of testicles
- Micropenis/cryptorchidism
What is the phenotype of estrogen insenstivity and aromatase deficiency syndromes?
Female hormones do play role in male sexual development
- If no aromatase, no production of estradiol
Results in:
- Tall stature; vertical growth continues into 30s, unfused epiphyses
- Genu valgum (knock-kneed)
- Osteoporosis
- Eunuchoid proportions of the skeleton
- Increased adiposity
- Acanthosis nigricans, insulin resistance
- NASH
Sometimes:
- Oligozoospermia
- Cryptorchidism
- Increased volume of testes
- Changes in sexual behavior
Epidemiology of Hypogonadism
- Prevalence
- 39% of population > 45 yo have lower testosterone than normal
- Diagnosis is made based on low T and symptoms (sexual, decreased strength, psychological) it was much lower in 40-70 yo pop
- Only a minority of men with hypogonadism are treated (5-10%)
What are signs and symptoms of androgen deficient states?
Development before birth first trimester
- Genital Ambiguity
Development before birth third trimester/after birth minipuberty
- Micropenis
Development before puberty
- Delayed puberty
- Lack of adult male hair distribution
- Decreased muscle mass and strength + increased subcutaneous fat
- Diminished endurance
- Decreased libido, ED
- No ejaculate
- Eunuchoid skeleton
- Infertility/Azoospermia
- Eunucoidism
- Small testes
- Loss of male hair
- Gynecomastia
- Osteoporosis
- Infantile genitalia and prostate
- High pitched voice
Development after puberty
- Incomplete sexual development
- Decreased libido and ED
- Decreased frequency of shaving
- Diminished body hair
- Decreased muscle mass and strength
- Diminished endurance
- Increased fat mass
- Gynecomastia
- Osteoporosis
- Infertility
- Testicular atrophy
- Small prostate
- Height loss for minimal trauma
- Hot flashes
What is Kallmann’s syndrome?
Autosomal dominant mutation in KAL gene
- Results in failure of proper migration in GnRH neurons and olfactory neurons
- Isolated hypogonadotropic hypogonadism with anosmia (Testosterone deficiency)
Gynecomastia facts
- Unilateral or symmetric?
- Relation to areola
- Discharge?
- Signs of possible malignancy
- Can be unilateral or asymmetrical
- Concentric in relationship to the areola and the consistency is moderately firm
- Rarely, one can express a milky discharge
Possible malignancy:
- Presence of blood in the discharge
- Skin dimpling
- Nipple retraction
- Harder consistency or axillary adenopathy
Drug induced gynecomastia can occur with what drugs?
