76. Adenohypophysis, the synthesis and release of the ACTH

Question 1

Hypophysis deficiency and overproduction

Answer 1

These symptoms will show by the removal or overactivity of the anterior pituitary, the hormone of this gland produced in the highest amount is growth hormone (STH or GH).

• removal of pituitary gland result in proportional dwarfism. In adulthood, as a result of its removal or hypofunctioning, organs become smaller, hairs become thin, and sexual functions decrease.
• In metabolism, the following changes can be observed: decreased protein and glycogen stores, saw- toothed fluctuation of plasma glucose levels, decreased basal metabolic rate.
• Congenital hyperpituitarism leads to gigantism, while hyperpituitarism in adult life results in acromegaly, which is the increase of the size of still enlargable extremities and other parts.

Question 2

Hormones of the hypophysis

Answer 2

Hypophyseal hormones are peptide (or protein) hormones and are synthesized by several adenohypophyseal cells.

-The group of GH, ACTH, TSH is usually called metabotropic hormones, whereas the group of PRL, FSH, LH is usually referred to as gonadotropic hormones.

Question 3

ACTH

Answer 3

ACTH, adrenocorticotrop hormone or corticotropin, is a polypeptide consisting of 39 amino acids, of which only 24 is responsible for the biological effect.

• ACTH stimulates glucocorticoid synthesis through increasing the c-AMP pathway.
• ACTH also increases aldosterone secretion.

Question 4

The synthesis of ACTH

Answer 4

• In the pituitary gland, more hormones are synthesized from a common precursor hormone: pre-proopiomelanocortin (Pre-POMC).
• Hormones derived from Pre-POMC are involved in adaptive processes of the organism. In case of stress, both ACTH and other peptides (endogenous opioid peptides) are released to mobilize energy reserves and to decrease sensation of pain very efficiently under stress.
• CRF (corticotropin releasing factor) of the hypothalamus stimulates all cleaving processes outlined below and, at the same time, it is a stimulator of POMC synthesis.

Question 5

The role of ACTH

Answer 5

• ACTH stimulates glucocorticoid synthesis in the layers of the adrenal cortex through the enhancement of the activity of cAMP pathway.
• In the glomerulosa layer this hormone has a less pronounced effect. It increases mineralocorticoid synthesis by increasing cholesterol - pregnenolone conversion.
• Since MSH is involved in the amino acid sequence of ACTH, enhanced ACTH level also results in a melanocyte stimulating activity. This phenomenon also contributes to the decoloration of the skin in Addison’s disease.

(in this syndrome, adrenal gland produces an insufficient amount of glucocorticoids, therefore the lack of inhibition through the negative feedback increases plasma ACTHto pathologic levels).

Question 6

Regulation of ACTH synthesis

Answer 6

• Synthesis of ACTH is regulated according to the classical feed-back principle.
• Not only the increasing glucocorticoid concentration is involved in this process (long feedback), but the inhibiting effect of ACTH on CRF is also of great importance (ultra short feedback).
• Various neural impulses reaching the hypothalamus (the inhibitory norepinephrine and GABA, or the excitatory serotonin and acetylcholine) are integrated by CRF synthesizing cells.
• CRF release is pulsatile and, ultimately, its circadian fluctuation determines the synthesis and secretion of ACTH.
• The extent of glucocorticoid production, stimulated by ACTH, elicits a negative feedback for ACTH synthesis through the blood circulation.

Question 7

Circadian rhythm of ACTH

Answer 7

• The half-life of ACTH is very short (approx. 15 min.), its concentration is significantly higher in early morning than late afternoon, it is the lowest by midnight, when decreased to a fraction of the early morning level. This is the cause of the daily fluctuation of glucocorticoid concentration (diurnal rhythm).
• Today it is known, that endogenous rhythm generators (suprachiasmatic nucl. and pineal gland) and environmental factors are responsible together for the fluctuation of hormone synthesis.