Jackson Lectures 6

Question 1

Congenital adrenal hyperplasia is an

Answer 1

adrenal enzyme deficiency results in excess production of adrenal androgens

Question 2

Congenital adrenal hyperplasia is caused by more than

Answer 2

one mutation and severity varies depending on mutation

Question 3

Congenital adrenal hyperplasia: example:

Answer 3

21α hydroxylase mutation impairs synthesis of cortisol → decreased negative feedback of cortisol on ACTH secretion → increased stimulation of adrenal cortex → increased production of adrenal androgens

Question 4

Congenital adrenal hyperplasia: genotype is

Answer 4

XX; phenotype is virilized or more male than female depending on severity

Question 5

5α-reductase deficiency (guevodoces): development of the

Answer 5

penis, scrotum and prostate gland is DHT-dependent

Question 6

5α-reductase deficiency (guevodoces): enzyme deficiecy results I failure of differentiation of the

Answer 6

external genitalia early in life, but increased T secretion with the onset of pubery completes differentiation.

Question 7

5α-reductase deficiency (guevodoces): phenotype is female at birth until

Answer 7

early puberty

Question 8

Testicular feminization or androgen insensitivity: lack

Answer 8

functional androgen receptor (used by both T and DHT)

Question 9

Testicular feminization or androgen insensitivity: no differentiation of

Answer 9

genitalia

Question 10

Testicular feminization or androgen insensitivity: genotype is

Answer 10

XY

Question 11

Testicular feminization or androgen insensitivity: phenotype is

Answer 11

female; condition often diagnosed at puberty

Question 12

There is a dramatic increase in circulating concentrations of steroid hormones during pregnancy due to

Answer 12

placental production

Question 13

CL regresses after

Answer 13

~ 3 months and hCG supports luteal steroidogenesis

Question 14

placental E2 stimulates

Answer 14

growth of myometrium

Question 15

placental P reduces

Answer 15

uterine contractility and stimulates vasodilation

Question 16

Endocrine regulation of growth

First, there are

Answer 16

non-endocrine factors that regulate growth

Question 17

Genetics is the principle factor controlling the potential for

Answer 17

growth.

Question 18

Disease damages tissue and activates the

Answer 18

HPA axis. Stress axis.
• This takes energy from growth processes
• Activates stress axis; cortisol inhibits growth

Question 19

cortisol inhibits

Answer 19

growth

Question 20

The hormones of the growth axis (GHRH → GH → IGF-1) control growth by their actions in

Answer 20

somatic tissue and the liver. (has direct actions in muscle, fat, and bone to stimulate growth)

Question 21

• The relative importance of

Answer 21

IGF-1 and GH varies during development.

Question 22

IGF-1 is necessary for

Answer 22

fetal growth; GH becomes important later in development.

Question 23

• IGF-1 is like insulin in terms of

Answer 23

structure, not action

Question 24

• Growth axis:

Answer 24

Hypothalamus, pituitary and muscle/fat/bone

Question 25

• Growth axis:

Answer 25

Hypothalamus, pituitary and muscle/fat/bone

Question 26

Thyroid hormone is required for synthesis of

Answer 26

GH and manifestation of GH effects. (permissive effect on GH)

Question 27

Growth is also controlled by

Answer 27

glucose-regulating hormones.

Question 28

Glucocorticoids inhibit

Answer 28

GHRH secretion.

Question 29

Insulin has actions that oppose

Answer 29

GH and IGF-1

Question 30

Gonadal steroids (T and E2) also have a role in growth. (conversion of testosterone to estradiol that causes

Answer 30

stoppage of growth)

Question 31

At puberty, the epiphyseal plates ossify due to the actions of

Answer 31

E2

Question 32

Lacks estradiol receptors (alpha receptor), kept on

Answer 32

growing

Question 33

GHRH – from hypothalamus, stimulate

Answer 33

GH secretion; comes from arcuate nucleus, stimulated with exercise, stress, fasting, sleep

Question 34

Somatostatin (SS) – inhibits

Answer 34

GH secretion, comes from paraventricular nucleus, but is secreted in pulsile manner of these hormones due to feedback mechanisms

Question 35

Need thyroxine to stimulate

Answer 35

growth

Question 36

GH also acts in somatic tissue (muscle and bone) to stimulate

Answer 36

protein synthesis. (Anabolic, does this through stimulation of AA uptake and ribosome stimulation)

Question 37

GH acts in opposition to

Answer 37

insulin (on muscle and fat); makes glucose available for growth

Question 38

The principle indirect effect of GH on growth is to stimulate the secretion of

Answer 38

insulin-like growth factor 1 (IGF-1, powerful mitogen) from the liver and other tissues (bone and cartilage). (stimulates gluconeogenesis)

Question 39

GH • LL feedback from

Answer 39

IGF-1

Question 40

• IGF-1 and GH inhibit

Answer 40

GH and GHRH secretion, but stimulate SS secretion (this will further decrease GH secretion)

Question 41

o GHRH elevated during

Answer 41

sleep, relative to day time levels

Question 42

o SS elevated during the

Answer 42

day

Question 43

Somatic growth is the result of interactions between

Answer 43

GH and IGF-1

Question 44

GH stimulates maturation of

Answer 44

chondroblasts into chondrocytes and upregulates IGF-1 receptor expression

Question 45

IGF-1 stimulates cell division (secreted by

Answer 45

chondrocytes)

Question 46

There are no known defects in

Answer 46

IGF-1 synthesis or for the IGF-1 receptor (insufficient IGF-1 is a lethal mutation)

Question 47

Malnutrition impairs IGF-1 synthesis independent of

Answer 47

GH

Question 48

Sex steroid stimulate

Answer 48

GH and IGF-1 synthesis, but have contrasting effects on skeletal growth.

Question 49

Steroids stimulate the

Answer 49

prepubertal spurt in bone growth, but ultimately causes fusion of the epiphyseal plates by inhibiting bone growth.

Question 50

Thyroid hormone regulates

Answer 50

GH synthesis, and is required for GH effects.

Question 51

Cortisol/glucocorticoids have

Answer 51

anti-growth effects. (inhibition of DNA synthesis; breakdown of bone, high levels of cortisol can inhibit growth axis)

Question 52

Glucocorticoid therapy- for things like asthma, you are impairing/inhibiting

Answer 52

growth due to effects of cortisol on growth axis