Biological functions and synthesis of Corticosterone

Corticosterone is the biological glucocorticoid in mice, rats, birds, reptiles, and amphibians, which do not have 17α-hydroxylase activity in the adrenal cortex. In these vertebrates, corticosterone is the primary glucocorticoid. In humans, corticosterone is an important intermediate in the synthesis of aldosterone from pregnenolone. As discussed in more detail in a later section, corticosterone also activates the MR and may function as a mineralocorticoid in the human brain and other organs that lack 11β- hydroxysteroid dehydrogenase-type 2, which inactivates corticosterone and cortisol. We note that in humans, cortisol is the main glucocorticoid. Corticosterone was isolated from adrenal glands; however, the glycogen retention and the antiinflammatory action of corticosterone are weaker than cortisol in humans. Corticosterone is synthesized in the zona fasciculata of the adrenal cortex, and converted into aldosterone via 18-hydroxycorticosterone in the zona glomerulosa.

Structural 

The synthesis of corticosterone begins with pregnenolone, which is converted to 11-deoxycorticosterone by two enzymes, 3β-hydroxysteroid dehydrogenase and 21α-hydroxylase, at the smooth endoplasmic reticulum. Then, in the final step, corticosterone is synthesized from 11-deoxycorticosterone by 11β-hydroxylase in the mitochondria in the zona fasciculata of the adrenal gland. In humans, corticosterone is an important intermediate in the steroidogenic pathway from pregnenolone to aldosterone.

Properties

Melting point: 179°C. Water solubility: 0.199mg/mL. 

Synthesis and release

Gene, mRNA, and precursor The human CYP11B1 gene, which catalyzes the synthesis of corticosterone from 11-deoxycorticosterone, is located on chromosome 8 (8q21), and consists of nine exons. The human CYP11B1 mRNA has 3534 bp, which encodes a protein of 503 residues.

Regulation of synthesis and release 

Rats, mice, birds, reptiles, and amphibians do not have 17α-hydroxylase activity, which catalyzes the conversion of 11-deoxycortisol to cortisol in the adrenal cortex. Corticosterone is the only glucocorticoid in these animals. Further, several studies show that stress increases the concentration of corticosterone in amphibians, reptiles, birds, and mammals.

Biological functions 

Physiological actions

Several studies indicate that endogenous corticosterone increases during stress.In amphibians, stressors elevate the plasma corticosterone levels. The administration of corticosterone induces hyperglycemia. Seasonal rhythms of corticosterone levels show the highest level during breeding.High levels of corticosterone can inhibit reproduction. Corticosterone can act as a competitor of androgens for the androgen receptor (AR). 

In reptiles,the seasonal pattern of corticosterone secretion generally shows a peak during the breeding season, although some species show no breeding increase and a few exhibit a decrease with breeding.

Although cortisol and corticosterone are glucocorticoids, some of their physiological functions are different. Both steroids play a basic role in the functions of the adrenal gland; however, these steroids have different effects on adrenal steroidogenesis. Cortisol inhibits 18-hydroxydeoxycorticosterone and aldosterone production in the tissue culture of adrenals, whereas corticosterone inhibits cortisol production and stimulates increased androgen production.Further, corticosterone plays different roles in the growth of undifferentiated and differentiated fetal rat adrenocortical cells; a low corticosterone concentration supports the proliferation of undifferentiated zona glomerulosa cells, and a high concentration inhibits the proliferation of differentiated zona fasciculata cells.

Son et al. reported that corticosterone directly induces the transcription of the gonadotropininhibitory hormone (GnIH) gene, which inhibits gonadotropin release from the anterior pituitary, by recruitment of the glucocorticoid receptor (GR) to its promoter.Mechanisms of actions During periods of stress, elevated corticosterone concentrations inhibit reproductive behaviors in amphibians, and this response to corticosterone is rapid.

Some genomic actions of corticosterone via the nuclear GR require hours to induce changes in transcriptional regulation. However, in some instances, corticosterone administration inhibits reproductive behaviors, including clasping, within a few minutes, suggesting that this rapid effect of corticosterone involves cell surface receptors.In general, corticosterone acts via the GR, although corticosterone also can activate the mineralocorticoid receptor (MR).For example the effects of corticosterone on blood pressure regulation within the hindbrain are mediated in part by the GR, but are also likely to involve MR-mediated effects.

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