LC Exam 1 Week 1 Flashcards
SRY gene location, function, and action
Short arm on Y chromosome
Sex determining region
Differentiation into testes at 7 wks
Important ovarian differentiation genes
RSPO1 and WNT4 lead to ß-catenin (inhibit testes promote ovary)
FOXL2
DAXI
Important genes for genital ridge formation
WT-1 (Wilms tumor)
WT-1 deletions lead to dysgenesis and Wilms tumor
NR5A1 aka SF-1
SF-1 deletions lead to gonad dysgenesis, adrenal failure, and persistent mullerian structures
Important testicular differentiation genes
SRY
SOX-9 (target of SRY)
Mesonephric and paramesonephric counterparts
Meso = Wolffian ducts (Epi, VD, SV) Para = Mullerian ducts (FT, uterus, upper vagina)
Male testicular sections in early development and cell that produces
Testosterone (Leydig) Antimullerian hormone (Sertoli)
External structure embryology male and female:
Genital tubercle
Urethreal folds
Labial/scrotal folds
GT: glands penis, clitoris
UF: penile urethra, labia minora
L/SF: scrotum, labia majora
Hymen
connection between genitourinary and Mullerian/vagina
Male development with testosterone
1st trimester: HCG stimulates Leydig cells
After: HPG axis required (hormone production starts around 10 wks)
External completed by 13 wks
4 steps in mullerian development
- Elongation
- Fusion
- Canalization
- Septal reabsorption
3 vaginal obstructions
- imperforate hymen (caudal end of sinovaginal bulb)
- transverse vaginal sinus (failed at vaginal plate)
- vaginal atresia (failed at UG sinus, below vaginal plate)
Class I mullerian defects: agenesis
4 types
Failure
Mullerian agenesis or hypoplasia
Vaginal, fundal, cervical, or tubal
Failed elongation
Class II mullerian defects: unicornuate
4 types
Failure
Unicornuate
Failure of one duct to reach UG sinus with contralateral duct
Communicating, non-communicating, no cavity, no horn
Failed elongation
Class III mullerian defects: didelphys
Pathophys
Failure
Uterine didelphys
Failure to fuse in the midline (failed fusion)
2 distinct cavities with longitudinal septum and two endometrial cavities and cervices
Longitudinal septum in vagina also common
Consequence of class III defect: didelphys
Obstructed hemivagina
Ipislateral renal anomaly
Progressive pain due to enlarging endo
Class IV mullerian defect: bicornate
2 types
Timing
Failure
Bicornate
Complete (extends to os) or partial (confined to fundus)
Occurs at 9th week gestation
Failure of fusion
Class V mullerian defect: septate
2 types
Failure
Septate
Complete (extends to os) or partial (confined to fundus)
Failed septal reabsorption
Most common abnormality, may be Asx.
Class VI and VII mullerian defects
VI: arcuate - no consequences
VII: DES exposure
Obstructive vs. non-obstructive congenital vaginal/uterine defects
Obstructive: cyclic pain
Non-obstructive: usually no pain
Treatment for failed vaginal canilization
DON’T ASPIRATE
Remove surgically
Neo vaginal options
- Vaginal dilators
2. Surgical plasty
Sertoli cell functions
Respond to FSH (GPCR)
Secrete AMH (degenerate mullerian)
Form blood sperm barrier
Secrete androgen binding protein (ABP): maintain high local T concentration for spermatogenesis
Convert androgen to estrogen via aromatase (also happens in adipose tissue)
Secrete inhibin (growth factor for Leydig, neg on FSH)
Leydig cell functions
Respond to LH (GPCR) Secrete testosterone (responsible for Wolffian) Secrete StAR and sterol carrier protein (steroidogenesis)
Male HPG feedback
Androgens: neg on GnRH and LH/FSH Estrogens: neg on LH/FSH Inhibin: neg on FSH IGF-1: stimulates GnRH T/E2: stimulate GH secretion
Actions of androgens in males
Differentiation of internal and external genitals
Initiation and maintenance of spermatogenesis
Development of 2ndary sex characteristics
Anabolic
Prepubertal vs. post pubertal FSH and LH levels in the male
Prepuberty: FSH>LH
Postpuberty: LH>FSH, due to preferential LH stimulation by GnRH and potentially inhibin release
Estrogen effects on bone growth
Stimulates bone growth
Accelerates maturation
Epi closure (narrows growth window)
Does Molly really smell like burritos?
Yes, but it’s kind of sexy
Venous drainage
Left ovary/testis: left gonadal vein, left renal vein, IVC
Right ovary/testis: right gonadal vein, IVC
Klinefelter syndrome: chr, pathophys, sx
47XXY
Dysgenesis of seminiferous tubules: low inhibin, high FSH
Abnormal Leydig: low T, high LH, high E2 conversion
Eunuchoid body, tall, gynecomastia, barr body, hypogonadism
Turner syndrome: chr, pathophys, sx
45XO
Menopause before menarche
Decreased E2 leads to increased FSH/LH
1˚ amenorrhea, preductal coarctation, cystic hygroma
Testosterone/LH levels in (and ex of): Defective androgen receptor Testosterone-secreting tumor, exo steroids 1˚ hypogonadism Hypogonadotropic hypogonadism
- AIS: increased T and LH
- Tumor/steroid: increased T and decreased LH
- Gonadal dysgenesis/failure: decreased T and increased LH
- Hypothalamus/pit dysfxn: decreased T and LH
46XX DSD: characteristics, example, hormone levels
Ovaries present, extgen is virilized or ambiguous
CAH, SRY translocation, ovotesticular
Exo androgens during pregnancy
46XY DSD: characteristics, example, hormone levels
Testes present, extgen is female/ambiguous
AIS (no sexual hair -vs mull agenesis-, increased T, E2, LH)
Androgen production problems:
5alpha reductase def
CAH/decreased sex hormones production: StAR or 17 anything
CAH: common types
- 21-hydroxylase
- 11-ß hydroxylase
- StAR (chole filled adrenal glands)
- 3ß-hydroxysteroid DH
- 17alpha hydroxlyase or 17,20 lyase
17 CAH and StAR with regards to DSD
Potassium status?
46XX DSD: Normal at birth, failure to develop 2ndary sex characteristic during puberty
46XY DSD: Undervirilized at birth
Hypokalemia in both
One CAH that produces undervirilized in males and virilized in females
3ß-hydroxysteroid DH
High block
Female puberty onset:
Breast tanner II
Menarche
Bone age
Breasts: 10.5 (earlier in Black/Hispanic)
Menarche: 12
Bone age: 10.5-11
Male puberty onset: Testes Pubic hair Penile enlargement Height velocity Bone age
Testes: 12 (9-14) Hair: 12 Enlargement: 13 Height velocity: 14 Bone age: 11.5-12
Congenital hypogonadatropic hypogonadism
Prader Willi
Kallman
Septo-optic-dysplasia
Idiopathic
Acquired hypogonadatropic hypogonadism
Pituitary/hypothalmic tumor
Cranial irradiation
CNS infection
AI hypophysitis
Hypergonadotropic hypogonadism
Primary ovarian and testicular failure
Klinefelters, Turners
Galactosemia
Cryptorchidism
Central precocious puberty
5% of girls = CNS abnormality 50% of boys = CNS abnormality Mass effect tumor Hydrocephalus Trauma Irradiation
Peripherial precocious puberty in females
Ovarian cyst Granulosa cell tumor Exogenous estrogens Lavendar products Severe primary hypothyroidism (TSH = FSH) - delayed bone growth
Peripherial precocious puberty in males
Adrenal tumor
Leydig cell tumor
Testotoxicosis: LH receptor mutation/activation
hCG secreting tumor
McCune Albright Syndrome
Late onset CAH
Severe primary hypothyroidism (TSH = FSH) - delayed bone growth
Evaluation of precocious puberty: LH and GnRH stim
Random LH: post-pubertal = central
Random LH: pre-pubertal = GnRH stim
Stim = pre-pubertal = peripheral
Stim = post-pubertal = central
Treatment of:
Central precocious puberty
Peripheral: ovarian cyst, McCune-Albright, testotoxicosis, CAH
Central: GnRH analogue Ovarian cyst: watchful wait/fu McCune: Aromatase inhibitor Testotoxicosis: Aromatase inhibitor + androgen blocker OR ketoconazole CAH: GC's
Lymph drainage
ovaries/testes: para-aortic lymph nodes
vagina/vulva/scrotum/anus: superficial inguinal
prostate/cervix/proximal vagina: deep inguinal
