Methods of treating overproduction of cortisol using ACTH antagonist peptides
View Patent ↗The present invention provides methods of treating overproduction of cortisol in a subject by administering to the subject a peptide that antagonizes adrenocorticotropin hormone (ACTH) to block the activation of melanocortin 2 receptors.
1. A method of treating a subject having a condition characterized by overproduction of cortisol, the method comprising administering to the subject an agent that significantly inhibits activation of a melanocortin 2 receptor (MC2R) without significantly inhibiting activation of a melanocortin receptor other than MC2R, wherein the agent is a polypeptide consisting of the amino acid sequence of KKRRPVKVYP (SEQ ID NO:1) or KKRRPVKVYPN (SEQ ID NO:2).
2. The method of claim 1 , wherein the agent is a polypeptide consisting of the amino acid sequence of SEQ ID NO:1.
3. The method of claim 1 , wherein the agent is a polypeptide consisting of the amino acid sequence of SEQ ID NO:2.
4. The method of claim 1 , wherein the agent reduces adrenocorticotropin hormone (ACTH)-induced production of cortisol by at least 10%.
5. The method of claim 1 , wherein the subject is a human.
6. The method of claim 1 , wherein the condition is selected from the group consisting of Cushing's syndrome, tumor of the anterior pituitary, chronic stress, and trauma.
7. The method of claim 6 , wherein the condition is Cushing's syndrome.
8. The method of claim 1 , wherein the agent is administered systemically.
9. The method of claim 1 , wherein the agent is administered by intravenous injection.
10. The method of claim 1 , wherein the agent is administered in a sustained release formulation.
11. A method of treating overproduction of cortisol in a population of non-human animals, the method comprising administering to the non-human animals an agent that significantly inhibits activation of a melanocortin 2 receptor (MC2R) without significantly inhibiting activation of a melanocortin receptor other than MC2R, wherein the agent is a polypeptide consisting of the amino acid sequence of KKRRPVKVYP (SEQ ID NO:1) or KKRRPVKVYPN (SEQ ID NO:2).
12. The method of claim 11 , wherein the non-human animals produce cortisol at a level that is associated with chronic stress in the non-human animals.
13. The method of claim 11 , wherein the agent is a polypeptide consisting of the amino acid sequence of SEQ ID NO:1.
14. The method of claim 11 , wherein the agent is a polypeptide consisting of the amino acid sequence of SEQ ID NO:2.
15. The method of claim 11 , wherein the agent reduces adrenocorticotropin hormone (ACTH)-induced production of cortisol by at least 10%.
16. The method of claim 11 , wherein the non-human animals are fish.
17. The method of claim 11 , wherein the non-human animals are chickens.
18. The method of claim 11 , wherein the agent is administered in a sustained release formulation.
19. A method of inhibiting adrenocorticotropin hormone (ACTH)-dependent activation of a melanocortin 2 receptor (MC2R), the method comprising contacting a cell expressing ACTH with a polypeptide consisting of the amino acid sequence of KKRRPVKVYP (SEQ ID NO:1) or KKRRPVKVYPN (SEQ ID NO:2); thereby inhibiting ACTH-dependent activation of the MC2R.
20. The method of claim 19 , wherein the cell is contacted with the polypeptide at a concentration sufficient to inhibit ACTH-dependent activation of the MC2R by at least 50%.
21. The method of claim 19 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:1.
22. The method of claim 19 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:2.