1. MCB 135E Discussion
October 3, 2005

2. Sex Differentiation: Male 6th Embryonal Week
Bipotential gonad differentiates as a testis & secretes testosterone (T) from Leydig cells
T secretion promotes:
Wolffian ducts differentiation
Male secondary sex organs
T secretion promotes:
Regression of Mullerian ducts by
Mullerian Inhibitory Substance (MIS)
from Sertoli Cells)
T secretion promotes:
Activity of 5 alpha reductase
to produce dihydrotestosterone (DHT)
and formation of external genitalia

3. Major Intersexual Conditions with NORMAL Chromosome Complement
Pseudohermaphroditism
A) Female
Congenital virilizing adrenal hyperlasia of the fetus
Maternal androgen excess:
Endogenous: virilizing adrenal or ovarian tumor
Exogenous: treatment with androgens or progestins
B) Male:
Androgen resistance
Defective testicular development
Congenital steroid enzyme deficiency
(lack of 5 alpha reductase)

4. Major Intersexual Conditions with ABNORMAL Chromosome Complement
1.Only one X or more than XX Chromosomes (female)
Ovarian dysgenesis XO (Turner’s Syndrome)
Superfemales XXX
2. With a Y and XX chromosome (male)
Seminiferous tubule dysgenesis XXY
(Klinefelters’s Syndrome)
3. Mosaics
True hermaphroditism

5. Example of Experimental Protocol

6. During Prenatal Growth
Studies from experimental animals show
that removal of the pituitary gland
(no GH, no T3, T4) or
damage to the hypothalamus
(no GHRH, GHIH, no TRH)
FAIL
to impair somatic body growth

7. During Prenatal Growth in humans
Infants born with:
*Pituitary aplasia
*Anencephaly
*Congenital GH deficiency
are all of normal size at birth
Maternal GH does NOT cross the placenta
Therefore maternal GH does not substitute for fetal GH

8. Fetal GH GH is secreted & circulates in blood
reaching a peak at midgestation
What is the function of fetal GH?
Perhaps
GH develops/differentiates those hypothalamic centers
regulating GHRH and GHIH
in readiness for their function after birth
Another example of the organizational actions of hormones

9. If GH does not regulate fetal growth then what does?
Insulin
may have an regulatory action on growth
*Detectable insulin blood levels at weeks
*Insulin receptors present by 15 weeks
*Levels rise progressively throughout gestation
*By 34 weeks, levels are more than 6x adult values

10. Insulin Insufficiency
Pancreatic agenesis (failure of pancreas development)
Leprechaunism (resembling elves)
Reduced intrauterine growth due to extreme insulin resistance
In both cases, the fetus at birth has low body weight
(decreased fat & decreased muscle mass)
These infants are hyperinsulinemic but their cells do not respond to insulin:
few receptors
less receptor binding
abnormal receptors
post receptor defects

11. Insulin-like Growth Factors (IGF1, IGF2)
IGFs: insulin-like peptides
mediate effect of GH on growth postnatally.
In adult, they are produced mostly in the liver,
simulated by GH.
In the human fetus levels of IGF1 are low.
However, fetal levels of IGF2 are as high as adult levels.
IGF1 levels are correlated with body weight
and increase at birth.