Fetal Endocrine and Autocrine/Paracrine-Acting Growth Factor Effects on Fetal Growth In IUGR.

 Fetal Endocrine and Autocrine/Paracrine-Acting Growth Factor Effects on Fetal Growth In IUGR.

Fetal hormones promote growth (and development) in utero by altering both the metabolism and gene expression of fetal tissues.

A.    Insulin:

Insulin has direct mitogenic effects on cellular development and cell number. It also enhances glucose consumption and limits protein breakdown. The latter effects are associated with reduced fetal growth when insulin concentration is low.

Thus, insulin deficiency, directly and indirectly, results in a decrease in fetal nutrient supply.

 

B.    Insulin-Like Growth Factor-I:

IGF-1 is a major anabolic hormone in fetal development. IGF-I is positively regulated by glucose supply in the fetus.

IGF-I probably can regulate metabolic processes that affect fetal protein balance and growth, but these have been difficult to measure.

Human IUGR fetuses have decreased plasma IGF-I concentrations.

Mutations in the Igf1 and Igf1r genes in humans cause both intrauterine and postnatal growth restriction.

C.    Thyroid Hormones:

In all species, fetal thyroid hormone deficiency or reduced free thyroxine (T4) produces developmental abnormalities in certain tissues and reduced growth.

Fetal hypothyroidism decreases oxygen consumption and oxidation of glucose, thereby potentially decreasing fetal energy supply for growth. Hypothyroidism also can decrease circulating and tissue concentrations of IGF-I.

D.    Cortisol:

Increasing fetal concentrations of cortisol near the end of gestation cause a switch in fetal tissues from accretion to differentiation and are important in the maturation of tissue-specific enzymatic pathways.

These include glycogen deposition, gluconeogenesis, fatty acid oxidation, induction of surfactant production and release, structural maturation of alveoli, structural maturation of the gastrointestinal tract, increased expression of digestive enzymes, increased adrenal function, switch from fetal to adult hemoglobin synthesis, and others.

Many IUGR fetuses have increased cortisol concentrations that appear to result from intermittent hypoxic stress.

Increased fetal cortisol concentrations may induce organ differentiation prematurely, which may account for much of the apparent increased maturation of IUGR fetuses, even when born preterm.

Cortisol also increases catabolic pathways in tissues, including protein breakdown in skeletal muscle and glycogenolysis in the liver, and can restrict placental growth and nutrient transport, which can result in reduced overall fetal growth rates.