Gonadal Differentiation and Intersex

Question 1

what is the role of sex determining region Y (SRY) protein in gonadal development?

Answer 1

is a DNA binding protein that initiates testes development, directing the bipotential gonads towards a male phenotype

Question 2

what is SF-1?

Answer 2

an important factor in gonadal and adrenal development, reproduction and anti-mullerian hormone regulation

Question 3

what are the consequences of mutations in SF-1?

Answer 3

lead to adrenal insufficiency in 46,XY females (resulting in low androgens) and gonadal dysgenesis

Question 4

what happens in cases of SRY translocation or mutation?

Answer 4

can lead to 46,XX males where sRy remains function, or 46,XY females due to loss of SRY function

Question 5

the presence of androgen in males induces what?

Answer 5

irreversible changes

Question 6

what irreversible changes to androgens induce in males?

Answer 6

genital differentiation and during puberty the development of secondary sex characteristics such as larger facial bones, hands, feet and increased height

Question 7

how do androgen levels affect genital differentiation and secondary sex characterisitcs in females?

Answer 7

allow for female genital differentiation and development of secondary sex charac

Question 8

what factors influence androgen/estrogen ratios?

Answer 8

genetic variations, hormonal imbalances, environmental exposures and medical conditions

Question 9

what influences testicular and ovarian differentiation?

Answer 9

combo of hormonal and environmental factors during embryonic development

Question 10

what is unique about the undifferentiated gonad?

Answer 10

able to develop into either testes or ovaries depending on the genetic and environmental cues present during development

Question 11

how many genes ID;d to regulate sex processes?

Answer 11

more than 50

Question 12

mullerian ducts

Answer 12

(or paramesonephric ducts) are paired ducts of the embryo that run down the lateral sides of the urogenital ridge.

Question 13

what do mullerian ducts develop into in females?

Answer 13

fallopian tubes, uterus and upper portion of the vagina

Question 14

what is the default form of mullerian ducts in the absense of androgen exposure?

Answer 14

female

Question 15

what are wolffian ducts?

Answer 15

paired organs found during embryogenesis, in males develop into the epididymis, vas deferens, and seminal vesicle

Question 16

what is critical for development of wolffian ducts?

Answer 16

exposure to testosterone during embryogenesis

Question 17

Anti-Müllerian hormone

Answer 17

(or Mullerian
Inhibiting Factor) (TGF-β family) produced by Sertoli cells and Leydig cells
control stabilization of Wolffian ducts

Question 18

what is amenorrhea

Answer 18

absense of menstrual cycle after the age of 16 or after three missed periods

• can be sign of genetic, endocrine or anatomic abnormalities

Question 19

what are some examples of conditions associated w amenorrhea

Answer 19

GnRH deficiency (such as Kallmann’s Syndrome), functional hypothalamic amenorrhea, and hyperprolactinemia

Question 20

what is kallmanns syndrome?

Answer 20

occurring in about 1 in 125,000 people, is characterized by a deficiency in GnRH due to a mutation in adhesion molecule genes. This results in the absence of sexual maturity and a sense of smell

Question 21

what are causes of hyperpolactinemia

Answer 21

reduced dopamine inhibition of prolactin release

Question 22

what is menopause

Answer 22

cessation of ovarian function, occuring at age 51

Question 23

sex refers to

Answer 23

biological and physiological characterisitcs that define men and women

Question 24

gender refers to

Answer 24

socially constructed roles, behaviours, etc

Question 25

intersex people are individuals…

Answer 25

born with any of
several variations in sex characteristics
including chromosomes, gonads, sex hormones
or genitals that, “do not fit the typical definitions
for male or female bodies“

Question 26

Klinefelter’s
Syndrome.
male 47,
XXY

Answer 26

Gonadal dysgenesis, low testosterone, sometimes
no clear 2nd-ary sex characteristics, there may be mental retardation (but rare).

1/500 males; most common form of male hypogonadism, and also is the most commonly
found human sex chromosomal abnormality. Low androgens.

Question 27

Turner’s Syndrome, female 45, X

Answer 27

Gonadal dysgenesis, almost no estrogen or progesterone, no sec sex char.; numerous developmental problems including short, web neck,
hearing and kidney loss of function

• Mostly fatal to fetus so only 1/5000
• Most often father did not pass on a sex chromosome
• Both treatable with hormones for secondary sexual characteristics, but will always be infertile

Question 28

Intersex 46, XY DSD (Formerly called Male pseudohermaphroditism)

Answer 28

have testes but genital ducts or external genitalia not fully masculinized

Question 29

defect in Testosterone (T) secretion

Answer 29

• testicular dysgenesis
• impaired T or MIF secretion
• Gonadal target tissue not responsive
• No T → DHT conversion (Also may lack 5α-reductase (5α-R), in this case with the no 5α-R, T would be normal)

Question 30

Androgen Insensitivity syndrome (AIS, Resistance)

Answer 30

Complete – 46, XY
* testes present, but absent wolffian ducts, female-appearing external genitalia
* at puberty, female 2° sex char, no menarche
* ↑ LH secretion → ↑ T and E2 (peripheral and testes)
* Androgen receptor mutation is common
Incomplete – variable presentation

Question 31

What are some causes of androgen biosynthetic dysfunction in 46, XY individuals?

Answer 31

Causes include mutations in the luteinizing hormone (LH) receptor (LHR), 17α-hydroxylase deficiency, and 5α-reductase deficiency, leading to decreased androgen production or inability to make certain androgens.

Question 32

What is the result of 17α-hydroxylase deficiency in 46, XY individuals?

Answer 32

17α-hydroxylase deficiency leads to the inability to produce androgens, which can result in ambiguous gonads or feminization, termed as intersex 46, XY DSD (previously called male pseudohermaphroditism).

Question 33

What is the consequence of 5α-reductase deficiency in 46, XY individuals?

Answer 33

5α-reductase deficiency prevents the conversion of testosterone to dihydrotestosterone (DHT), resulting in incomplete masculinization and ambiguous genitalia, termed as 46, XY DSD (previously called male pseudohermaphroditism).

Question 34

What conditions lead to androgen excess in 46, XX individuals?

Answer 34

Androgen excess in 46, XX individuals can be caused by 21α-hydroxylase deficiency, aromatase deficiency, or increased androgen exposure in utero, resulting in masculinization or ambiguous genitalia, termed as intersex 46, XX DSD (previously called female pseudohermaphroditism).