81. Synthesis, regulation and physiological effects of glucocorticoids

Question 1

Adrenal cortex

Answer 1

Adrenal glands are paired, compound organs. The adrenal cortex makes up 95 % of the gland. while the medulla located inside, it is a part of the sympathetic nervous system.Adrenal cortex plays a crucial role in mineral and water metabolism, as well as in mobilization of energy stores of the body. -Hormones of the cortex belong to the steroid group. These are mineralocorticoids (mostly aldosterone) and glucocorticoids (cortisol, corticosterone). -Catecholamines are synthesized in the medulla (their major representatives are epinephrine and norepinephrine).

Question 2

Morphology

Answer 2

There are three zones of the adrenal cortex:

(1) z. glomerulosa in ruminants ( horse, donkey, carnivores, pig: z. arcuata) ,
(2) z. fasciculata and
(3) z. reticularis.
- Cells of the cortex and the medulla are mixed up. In fetal age, there is a so called X-zone inside, it is involved in fetal corticoid synthesis.
- Cells contain a high amount of fat, cholesterol, phospholipids and ascorbic acid.

Question 3

There are three groups of formones of the adrenal cortex

Answer 3

There are three groups separated according to the number of carbon atoms:

– The frame of corticosteroids is a 21-carbon pregnane. Mineralocorticoids and glucocorticoids belong to this group.

– Androgenic steroids can be derived from the androstane (19C) frame. Male sexual hormones belong to this group, which are mainly produced by the testes and adrenal cortex, although, in smaller amount, they are also synthesized in the ovary and placenta.

– Estrogen steroids belong to the group of compounds derived from the 18-carbon estrane frame. These are female sexual steroids. Ovary, or - in lesser extent - the adrenal cortex, testes and placenta, are both involved in their synthesis.

Question 4

Physiological effects of glucocorticoids

Answer 4

Cortisol and corticosterone are the most prominent glucocorticoids.

The outstanding physiological effect of the glucocorticoids is the long lasting mobilization of the energy reserves of the body.

Anti-inflammatory and immunosuppressive.

Question 5

Metabolic effects of glucocorticoids

Answer 5

• Amino acids are transported to the liver for intake. Amino acid mobilization increases. GNG is so excessive, that steroid diabetes develops. In case of prolonged effect, diabetes persists: metasteroid diabetes is formed. This is effectively intensified by the antiinsulin effect of glucocorticoids.
• Glucocorticoids decrease protein synthesis and increase protein cleaving in every tissue. Nitrogen balance becomes negative, even in the well-fed animal. As a final outcome of these processes, there are enough free amino acids available for GNG.
• These hormones effectively increase lipolysis, plasma level of FFAs, and extent of fat burning.
• Since synthetic processes are less inhibited in the liver, adipose deposits are displaced from periphery to the liver. This is called “redistribution” of fat. From household or veterinary points of view, this phenomenon has a great significance. If an animal suffers a prolonged burden (e.g. hunger, or other stress) continuous glucocorticoid treatment increases fat deposition in the liver so much, that can cause the death of the animal (bovine fatty liver 275 syndrome!).

Question 6

Production:

Answer 6

In the case of the glucocorticoid producing z. fasciculata, the basis of the regulation is the hypothalamic-pituitary (CRF - ACTH) control. The role of glucocorticoids is determinant in the feedback (long feedback loop).

The basis of steroid hormone production is LDL intake from the plasma. It is a source of cholesterol synthesis in 80 %. However, 20% of the cholesterol is synthesized locally, de novo.

Question 7

Synthesis

Answer 7

Basic synthetic pathways, their key enzymes, and structure of the most important steroid hormones are depicted:

1. 20, 22 demolase enzyme, the key enzyme of the entire steroid synthesis. Side chain cleavage enzyme. This enzyme, as most of the enzymes of the steroid synthesis, belong to the P450 enzyme family.
2. 3-beta-hydroxysteroid dehydrogenase-4-5-isomerase enzyme. Lack of this enzyme leads to fatal consequences, for neither mineralocorticoids nor glucocorticoids are produced.
3. 17-alpha-hydroxylase enzyme determines glucocorticoid direction. In the lack of it a considerable overproduction of aldosterone and corticosterone takes place: synthesis of typical glucocorticoids is stopped, there is also no synthesis of androgens or estrogens.

Question 8

Lack

Answer 8

Since these key enzymes are responsible for only certain synthetic pathways (mineralocorticoid, glucocorticoid, or sexual steroid pathways), their dysfunction results in the lack of only certain hormone-families. Because of the negative feedback, many other types of hormones may significantly accumulate.