Fetal and neonatal physiology

The endocrine regulation of growth

89,90

Hormone secretion of the fetus

Maternal steroid hormones and thyroid hormones cross the placenta.

Pancreas: Insulin/Glucagon (8th week) Diabetes mellitus of the mother!

Thyroid hormones: (10th week) Cretinism!

Adrenal cortex: (16th week) Androgens

Cortisol Surfactant

Testis: (8th week) Testosterone, Müllerian duct regression factor

Makrosomie (over 5 kg birth weight)

Fetal circulation

HbF (α2γ2)

HbF exhibits a low affinity

for 2,3-DPG

+

Higher Hb concentration

Botalli

Arantii

vascular resistance is high in the lung

(hypoxic pulmonary vasoconstriction)

Umbilical

vein

Umbilical

arteries

upper part

of the body

lower part

of the body

right

ventricle

gut

O2 saturation (%)

% of cardiac output

liver

Placenta

Breathing

1) increase in the surface area available for gas exchange

2) fall in pulmonary vascular resistance

ad 1) Amniotic fluid is pressed out by the birth process.

Mild hypoxia and hypercapnia, as well as cold skin trigger the first breath.

Amniotic fluid is absorbed from the respiratory system (reabsorption of Na+ and water).

+Surfactant production

Perfusing its body by breathing independently instead of utilizing placental

oxygen is the first challenge of a newborn.

ad 2) Breathing increases pO2 in the lung, that dilates pulmonary blood vessels.

Local release of endothelial prostacyclin and NO.

At birth removal of the placental

circulation increases systemic

vascular resistance, whereas

pulmonary expansion decreases

pulmonary vascular resistance.

At birth left atrial pressure begins

to exceed the right atrial pressure,

causing the foramen ovale to

close.

Closure of the ductus arteriosus

completes the separation between

pulmonary and systemic

circulation (reduced prostaglandin

E2 levels).

Changes in the circulation at and around birth

before birth after birth

Breathing improves blood gas parameters.

Arterial pO2 increases from approx. 25-30 to 80-100 mmHg

Arterial O2 saturation increases from approx. 60% to 95%

Switch from fetal HbF to adult HbA hemoglobin.

Neonatal jaundice (Icterus neonatorum)

Most infants develop visible jaundice due to elevation of

unconjugated bilirubin concentration during their first week.

Relatively low activity of the enzyme glucuronosyltransferase

which normally converts unconjugated bilirubin to conjugated

bilirubin that can be excreted into the gastrointestinal tract.

In phototherapy, blue light is typically used.

„Kernicterus” is a bilirubin-induced brain dysfunction: the

blood–brain barrier is not fully functional in neonates and

therefore bilirubin is able to cross the barrier.

Regulation of growth Fertilized egg adult person

Hyperplasia: increase in number of cells

Hypertrophy: enlargement of cells

+ Differentiation

Intrauterine growth: (approx. 50 cm)

Genetic information

Maternal environment (nutrition, drugs, alcohol)

Metabolic (eg. diabetes mellitus of the mother)

Hormones

Insulin

Insulin-like growth factor-2 (IGF-2)

Human placental lactogen

(Thyroid hormones)

Extrauterine growth:

Growth hormone

Insulin-like growth factor-1 (IGF-1)

Androgens, estrogens

Hormones regulating Ca++ (Parathormone, Calcitonin, Calcitriol)

Thyroid hormones (GH synthesis )

Glucocorticoids (oversecretion inhibits normal growth)

Cretinism

Growth factors

1) Increasing cell mass by stimulating the production and/or inhibiting the

degradation of macromolecules

2) Increasing cell number by stimulating the rate of cell division, referred to as

mitogenic activity

3) Increasing cell number through increased cell survival due to inhibition of

apoptosis

Epidermal growth factor

Fibroblast growth factor

Platelet derived growth factor

Insulin-like growth factors

Nerve growth factor

Growth hormone receptor signalling pathways.

Reprinted from TRENDS in Endocrinology and Metabolism 12(6), J. Herrington and C. Carter-Su, Signaling

pathways activated by the growth hormone receptor, 252-257, 2001, with permission from Elsevier,

The activated JAK2 molecule

phosphorylates itself and the

cytoplasmic domain of the GH

receptor on tyrosine residues.

These phosphotyrosines form

binding sites for signaling

proteins.

Growth hormone receptor

Growth hormone (GH)

Janus

Homology between GH, prolactin and hPL

Secreted in the acidophilic cells (40 % of the anterior pituitary)

Phosphorylation

+

New protein synthesis

Growth hormone

Polypeptide (191 amino acids)

Effects:

Metabolic effects

Protein metabolism: synthesis of proteins (anabolic effect)

Fat metabolism: mobilization of stored fat (lipolysis)

Carbohydrate metabolism:

„anti-insulin” effect:

decreased insulin sensitivity of cells

decreased glucose uptake into some tissues

increased hepatic glucose output

Growth promoting effect

Liver (muscle, kidney etc.):

secretion of somatomedins (Insulin-like growth factors)

„insulin-like” activity

increased glucose uptake

increased protein synthesis

stimulated chondrocyte proliferation

doping

Somatomedin - Insulin-like growth factor

Insulin-like growth factor-1 (IGF-1) Insulin-like growth factor-2 (IGF-2)

Polypeptide

It is secreted by the liver and other tissues in response to stimulation by growth

hormone.

While GH appears to be the main regulator of the IGF-1 gene, control over the IGF-2 gene is less clear.

(IGF-2 regulates growth of the fetus before birth.)

liver

pre-pro-IGF-1

pre-pro-IGF-2

Growth hormone-releasing hormone

Growth hormone-

inhibiting hormone

epiphyseal

growth

Liver

Lipolysis

Glykogenolysis

Protein synthesis

glucose

amino acids

free fatty acids

GHRH

Inheritance,

exercise, sleep, stress

Estrogens

Androgens

Growth hormone

stomach

hours

GH

GHRH

Somatostatin

10 p.m. 10 a.m.

T3, T4

Overproduction of growth hormone

Childhood:

Gigantism

Adulthood:

Acromegaly

Growth hormone deficiency

Childhood:

Dwarfism (proportional)

Adulthood:

metabolic symptoms

17.09.2009. Guinness World Record

8.2. 2011. 251 cm

Enlargement of hands and feet (increase in ring size

and shoe size)

Increased prominence of jaw and/or forehead

Thickened skin

Hyperglycemia

(Stimulation of prolactin receptors)

overuse of growth hormone

Laron-dwarfs

Pygmy is a term used for various ethnic groups whose average height is unusually

short; adult men grow to less than 150 cm in average height.

Pygmy peoples

Growth percentile chart is to compare a child’s weight and

height percentile to the average child

Extracted growth hormone was used

since late 1950s until late 1980s when

its use was replaced by recombinant

GH.

Growth Hormone therapy

beginning

of the therapy

7 11 years