Hormone corticotrope

The hormone corticotrope or ACTH ( Adreno CorticoTropic Hormone ) is a polypeptide Hormone, mainly secreted by the basophilic cells of the former lobe of the Hypophyse and which stimulates the corticosuprarenal gland. It is the product of maturation of a pro-hormone, POMC (pro-opiomélanocortine).

Structure

The ACTH is a polypeptide made up of 39 Amino-acid , of which the 24 first never vary, the others variable according to the species.

Below, the sequence of the amino-acids at the man:
Ser-Tyr-Ser-Put-Lime-His-Phe-Arg-Try-Gly-Lily-Pro-Valley-Gly-Lily-Lily-Arg-Arg-Pro-valley-
Lys-Val-Tyr-Pro-Asp-Ala-Gly-Glu-Asp-Glu-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH

Effects

The ACTH stimulates the three zones of the cortex of the Glande Surrénale:

the glomérulée zone, which produces the Minéralocorticoïde S: Aldosterone and Corticostérone.
the fascicular zone, which produces the Glucocorticoïde S: Cortisol.
the reticular zone, which produces the Androgène S: DHEA (déhydroépiandrostérone), androstènedione.

Regulation

The Hypothalamus secretes three hormones known as Sécrétagogue S, which are the Corticotropin-releasing hormone (CRH), the Vasopressine, and PACAP ( Pituitary Adenylate cycle-Activating Peptide ). These hormones are able to activate, thanks to different Second intracellular messengers, the synthesis of gene of POMC (pro-opiomélanocortine), precursory polypeptide of the ACTH, like its maturation by various enzymes (the pro-hormones convertases), and the secretion of the ACTH stored on the level of the Hypophyse. In situation of Stress physical or psychological (infection, fever, pain, tiredness, fear or temperature variation), the secretion of CRH in particular is strongly increased, which, via the ACTH, induced a release of Glucocorticoïde S on the level of the glands surénales.

Conversely, there exists a negative Rétrocontrôle by the glucocorticoïdes, which act mainly on the pituitary gland by inhibiting the form of gene of the POMC and by blocking the release of ACTH in blood circulation. The glucocorticoïdes inhibit also upstream, the synthesis of the three hormones sécrétatogues on the level of the hypothalamus and block the secretion of the stored CRH.

Mode of action

The ACTH is a hormone at circadian rate/rhythm and pulsatile secretion, c.a.d. variable according to the hour of the day and the night. Its blood concentration is maximum right before the peak of Cortisol being at the man before the alarm clock (towards 6:00 of the morning), and minimal the evening (towards 23:00) before laying down it. It should be noted that in the night animals (rodent…) the peaks are reversed (maximals towards 20:00 and minimals towards 7:00). The ACTH is fixed on membrane receivers of corticosuprarenal gland. This connection involves an increase in the intracellular concentration in AMPc, then a protein kinases activation which, in their turn, activates the enzymes responsible for the transformation of the Cholestérol into Prégnénolone, a common precursor of the Glucocorticoïde S and Minéralocorticoïde S.

Physiopathology

There exists a relatively frequent pathology called Syndrome of Cushing or chronic hypercortisolism. In 20 to 30% of the cases, this pathology is directly related to a deregulation of the secretion of ACTH is because:

- hypophyseal adenomata (one will speak then about Maladie of Cushing). That accounts for 50 to 60% of the syndromes of Cushing.

- ectopic secretions (" out of the lieu") ACTH by tumors more or less bénines (carcinoïdes bronchial, 60% of the cases ectopic) or really malignant (bronchial tumors with small cells, 10-20% of the cases ectopic), by tumors of the Pancreas, or Phéochromocytome S. the whole of ectopic secretions of ACTH accounts for 20% of the syndromes of Cushing.

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