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May 1972, Vol 105, No. 5 >
Article | May 1972

Decreased Cyclic AMP in the Epidermis of Lesions of Psoriasis

John J. Voorhees, MD; Elizabeth A. Duell, PhD; Lawrence J. Bass, MD; John A. Powell, MD; E. Richard Harrell, MD
[+] Author Affiliations

Accepted for publication Feb 22, 1972.

Read in part before the Workshop on Cell Controls in Psoriasis, National Institutes of Health, Bethesda, Md, 1971; and in part before the American Society for Experimental Pathology at the 56th FASEB annual meeting, Atlantic City, NJ, 1972.

Reprint requests to Department of Dermatology, University of Michigan Medical School, R6558 Kresge Medical Research Bldg, Ann Arbor, Mich 48104 (Dr. Voorhees).


Ann Arbor, Mich

From the Department of Dermatology, University of Michigan Medical School, Ann Arbor.


Arch Dermatol. 1972;105(5):695-701. doi:10.1001/archderm.1972.01620080025008
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Comments

Previously we suggested that incomplete differentiation, accelerated proliferation and glycogen accumulation in epidermis of psoriatic lesions might be due to deficient adenosine 3',5'-monophosphate (cyclic AMP) in epidermis of the lesion. Therefore, we measured endogenous cyclic AMP in involved and uninvolved epidermis of 25 psoriasis patients and normal epidermis of 25 control subjects. A statistically significant decrease in cyclic AMP was found in involved psoriatic epidermis when compared with uninvolved psoriatic and control epidermis. Because cyclic AMP regulates glycogen metabolism and promotes differentiation of cancer cells in culture while limiting their proliferation, the cyclic AMP deficiency may play a pathophysiological role in the rapid epidermal cell cycle kinetics of psoriasis. Therefore, topical application of cyclic AMP analogues or agents which promote cyclic AMP synthesis or retard its hydrolysis might be used therapeutically to either normalize psoriatic differentiation or prevent psoriasis from occurring.

REFERENCES

1 +
Lobitz WC Jr, Brophy D, Lamer AE, et al:  Glycogen response in human epidermal basal cell . Arch Derm 86:207-211, 1962;.
2 +
Freinkel RK:  Carbohydrate metabolism in the skin , in Montagna W, Lobitz WC Jr (eds): The Epidermis . New York, Academic Press Inc, 1964;, chap 24, pp 485-492.
3 +
Weinstein GD, Frost P:  Abnormal cell proliferation in psoriasis . J Invest Derm 50:254-259, 1968;.
4 +
Halprin KM, Ohkawara A:  Carbohydrate metabolism in psoriasis: An enzymatic study . J Invest Derm 46:51-68, 1966;.
5 +
Braun-Falco 0:  The histochemistry of psoriasis . Ann NY Acad Sci 73:936-976, 1958;.
6 +
Pinkus H, Mehregan AH: A Guide to Dermatohistopathology . New York, Appleton-Century-Crofts Inc, 1969;, pp 95-96.
7 +
Lever WF: Histopathology of the Skin , ed 4. Philadelphia, JB Lippincott Co, 1967;, p 101.
8 +
Goltz RW, Fusaro RM, Jarvis J:  Observations on glycogen in epithelial tumors . J Invest Derm 31:331-341, 1958;.
9 +
Voorhees JJ, Duell EA, Kelsey WH, et al:  Regulation of epidermal proliferation in vitro by epinephrine, adenyl cyclase and cyclic AMP, abstracted . Fed Proc 30:687, 1971;.
10 +
Voorhees J, Duell E, Kelsey W, et al:  The epinephrine-chalone, adenyl cyclase, phosphodiesterase cascade in the in vitro control of epidermal growth , abstracted. Clin Res 19:365, 1971;.
11 +
Voorhees JJ, Duell EA:  Psoriasis as a possible defect of the adenyl cyclase-cyclic AMP cascade . Arch Derm 104:352-358, 1971;.
12 +
Powell JA, Duell EA, Voorhees JJ:  Beta adrenergic stimulation of endogenous epidermal cyclic AMP formation . Arch Derm 104:359-365, 1971;.
13 +
Duell EA, Voorhees JJ, Kelsey WH, et al:  Isoproterenol-sensitive adenyl cyclase in a particulate fraction of epidermis . Arch Derm 104: 601-610, 1971;.
14 +
Voorhees JJ, Duell EA, Bass LJ, et al:  Inhibition of epidermal cell division by isoproterenol, dibutyryl cyclic AMP, and theophylline . Clin Res 19:682, 1971;.
15 +
Voorhees JJ, Duell EA, Kelsey WH:  Dibutyryl cyclic AMP inhibition of epidermal cell division . Arch Derm 105:384-386, 1972;.
16 +
Hsie AW, Jones C, Puck TT:  Further changes in differentiation state accompanying the conversion of Chinese hamster cells to fibroblastic form by dibutyryl adenosine cyclic 3',5'-monophosphate and hormones . Proc Nat Acad Sci USA 68:1648-1652, 1971;.
17 +
Bonner JT:  Aggregation and differentiation in the cellular slime molds , in Clifton CE, Raffel S, Starr MP (eds): Annual Review of Microbiology . Palo Alto, Calif, Annual Reviews Inc, 1971;, vol 25, pp 75-92.
18 +
Johnson GS, Friedman RM, Pastan I:  Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3',5'-cyclic monophosphate and its derivatives . Proc Nat Acad SciUSA 68:425-429, 1971;.
19 +
Prasad KN, Hsie AW:  Morphologic differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3',5'-cyclic monophosphate . Nature New Biology 233:141-142, 1971;.
20 +
Gilman AG, Nirenberg M:  Regulation of adenosine 3',5'-cyclic monophosphate metabolism in cultured neuroblastoma cells . Nature 234:356-358, 1971;.
21 +
Sheppard JR:  Restoration of contact-inhibited growth to transformed cells by dibutyryl adenosine 3',5'-cyclic monophosphate . Proc Nat Acad Sci USA 68:1316-1320, 1971;.
22 +
Robison GA, Butcher RW, Sutherland EW:  Cyclic AMP , in Boyer PD, Meister A, Sinsheimer RL, et al (eds): Annual Review of Biochemistry . Palo Alto, Calif, Annual Reviews Inc, 1968;, vol 37, pp 149-174.
23 +
Stewart WD, Runikis JO:  Metabolically active skin slices . J Invest Derm 49:159-164, 1967;.
24 +
Marrs JM, Voorhees JJ:  A method for bioassay of an epidermal chalone-like inhibitor . J Invest Derm 56:174-181, 1971;.
25 +
Lowry OH, Rosebrough NJ, Farr AL, et al:  Protein measurement with the folin phenol reagent . J Biol Chem 193:265-275, 1951;.
26 +
Hennings H, Elgjo K:  Epidermal regeneration after cellophane tape stripping of hairless mouse skin . Cell Tissue Kinet 3:243-252, 1970;.
27 +
Burton K:  Determination of DNA concentration with diphenylamine , in Grossman L, Moldave K (eds): Methods in Enzymology . New York, Academic Press Inc, 1968;, vol 12, pt (B) , pp 163-165.
28 +
Breckenridge BM:  Methods of assay of cyclic nucleotides , in Robinson GA, Nahas GG, Triner L (eds): Cyclic AMP and Cell Function . New York, New York Academy of Sciences, 1971;, vol 185, pp 10-17.
29 +
Goldberg ND, O'Toole AG:  Analysis of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate , in Glick D (ed): Methods of Biochemical Analysis , New York, John Wiley & Sons Inc, 1971;, vol 20, pp 1-39.
30 +
Brooker G, Thomas LJ Jr, Appleman MM:  The assay of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate in biological materials by enzymatic radioisotopic displacement . Biochemistry 7:4177-4181, 1968;.
31 +
Liddle GW, Hardman JG:  Cyclic adenosine monophosphate as a mediator of hormone action . New Eng J Med 285:560-566, 1971;.
32 +
Otten J, Johnson GS, Pastan I:  Cyclic AMP levels in fibroblasts: Relationship to growth rate and contact inhibition of growth . Biochem Biophys Res Comm 44:1192-1198, 1971;.
33 +
Gilman AG:  A protein binding assay for adenosine 3',5'-cyclic monophosphate . Proc Nat Acad Sci USA 67:305-312, 1970;.
34 +
Robison GA, Butcher RW, Sutherland EW:  Some actions of cyclic AMP , in Cyclic AMP . New York, Academic Press Inc, 1971;, chap 5, pp 128-136.
35 +
Heidrick ML, Ryan WL:  Adenosine 3',5' cyclic monophosphate and contact inhibition . Cancer Res 31:1313-1315, 1971;.
36 +
Masui H, Garren LD:  Inhibition of replication in functional mouse adrenal tumor cells by adrenocorticotropic hormone mediated by adenosine 3',5'-cyclic monophosphate . Proc Nat Acad Sei USA 68:3206-3210, 1971;.
37 +
Muneyama K, Bauer RJ, Shuman DA, et al:  Chemical synthesis and biological activity of eight-substituted adenosine 3',5'-cyclic monophosphate derivatives . Biochemistry 10:2390-2395, 1971;.

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1 +
Lobitz WC Jr, Brophy D, Lamer AE, et al:  Glycogen response in human epidermal basal cell . Arch Derm 86:207-211, 1962;.
2 +
Freinkel RK:  Carbohydrate metabolism in the skin , in Montagna W, Lobitz WC Jr (eds): The Epidermis . New York, Academic Press Inc, 1964;, chap 24, pp 485-492.
3 +
Weinstein GD, Frost P:  Abnormal cell proliferation in psoriasis . J Invest Derm 50:254-259, 1968;.
4 +
Halprin KM, Ohkawara A:  Carbohydrate metabolism in psoriasis: An enzymatic study . J Invest Derm 46:51-68, 1966;.
5 +
Braun-Falco 0:  The histochemistry of psoriasis . Ann NY Acad Sci 73:936-976, 1958;.
6 +
Pinkus H, Mehregan AH: A Guide to Dermatohistopathology . New York, Appleton-Century-Crofts Inc, 1969;, pp 95-96.
7 +
Lever WF: Histopathology of the Skin , ed 4. Philadelphia, JB Lippincott Co, 1967;, p 101.
8 +
Goltz RW, Fusaro RM, Jarvis J:  Observations on glycogen in epithelial tumors . J Invest Derm 31:331-341, 1958;.
9 +
Voorhees JJ, Duell EA, Kelsey WH, et al:  Regulation of epidermal proliferation in vitro by epinephrine, adenyl cyclase and cyclic AMP, abstracted . Fed Proc 30:687, 1971;.
10 +
Voorhees J, Duell E, Kelsey W, et al:  The epinephrine-chalone, adenyl cyclase, phosphodiesterase cascade in the in vitro control of epidermal growth , abstracted. Clin Res 19:365, 1971;.
11 +
Voorhees JJ, Duell EA:  Psoriasis as a possible defect of the adenyl cyclase-cyclic AMP cascade . Arch Derm 104:352-358, 1971;.
12 +
Powell JA, Duell EA, Voorhees JJ:  Beta adrenergic stimulation of endogenous epidermal cyclic AMP formation . Arch Derm 104:359-365, 1971;.
13 +
Duell EA, Voorhees JJ, Kelsey WH, et al:  Isoproterenol-sensitive adenyl cyclase in a particulate fraction of epidermis . Arch Derm 104: 601-610, 1971;.
14 +
Voorhees JJ, Duell EA, Bass LJ, et al:  Inhibition of epidermal cell division by isoproterenol, dibutyryl cyclic AMP, and theophylline . Clin Res 19:682, 1971;.
15 +
Voorhees JJ, Duell EA, Kelsey WH:  Dibutyryl cyclic AMP inhibition of epidermal cell division . Arch Derm 105:384-386, 1972;.
16 +
Hsie AW, Jones C, Puck TT:  Further changes in differentiation state accompanying the conversion of Chinese hamster cells to fibroblastic form by dibutyryl adenosine cyclic 3',5'-monophosphate and hormones . Proc Nat Acad Sci USA 68:1648-1652, 1971;.
17 +
Bonner JT:  Aggregation and differentiation in the cellular slime molds , in Clifton CE, Raffel S, Starr MP (eds): Annual Review of Microbiology . Palo Alto, Calif, Annual Reviews Inc, 1971;, vol 25, pp 75-92.
18 +
Johnson GS, Friedman RM, Pastan I:  Restoration of several morphological characteristics of normal fibroblasts in sarcoma cells treated with adenosine-3',5'-cyclic monophosphate and its derivatives . Proc Nat Acad SciUSA 68:425-429, 1971;.
19 +
Prasad KN, Hsie AW:  Morphologic differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3',5'-cyclic monophosphate . Nature New Biology 233:141-142, 1971;.
20 +
Gilman AG, Nirenberg M:  Regulation of adenosine 3',5'-cyclic monophosphate metabolism in cultured neuroblastoma cells . Nature 234:356-358, 1971;.
21 +
Sheppard JR:  Restoration of contact-inhibited growth to transformed cells by dibutyryl adenosine 3',5'-cyclic monophosphate . Proc Nat Acad Sci USA 68:1316-1320, 1971;.
22 +
Robison GA, Butcher RW, Sutherland EW:  Cyclic AMP , in Boyer PD, Meister A, Sinsheimer RL, et al (eds): Annual Review of Biochemistry . Palo Alto, Calif, Annual Reviews Inc, 1968;, vol 37, pp 149-174.
23 +
Stewart WD, Runikis JO:  Metabolically active skin slices . J Invest Derm 49:159-164, 1967;.
24 +
Marrs JM, Voorhees JJ:  A method for bioassay of an epidermal chalone-like inhibitor . J Invest Derm 56:174-181, 1971;.
25 +
Lowry OH, Rosebrough NJ, Farr AL, et al:  Protein measurement with the folin phenol reagent . J Biol Chem 193:265-275, 1951;.
26 +
Hennings H, Elgjo K:  Epidermal regeneration after cellophane tape stripping of hairless mouse skin . Cell Tissue Kinet 3:243-252, 1970;.
27 +
Burton K:  Determination of DNA concentration with diphenylamine , in Grossman L, Moldave K (eds): Methods in Enzymology . New York, Academic Press Inc, 1968;, vol 12, pt (B) , pp 163-165.
28 +
Breckenridge BM:  Methods of assay of cyclic nucleotides , in Robinson GA, Nahas GG, Triner L (eds): Cyclic AMP and Cell Function . New York, New York Academy of Sciences, 1971;, vol 185, pp 10-17.
29 +
Goldberg ND, O'Toole AG:  Analysis of cyclic 3',5'-adenosine monophosphate and cyclic 3',5'-guanosine monophosphate , in Glick D (ed): Methods of Biochemical Analysis , New York, John Wiley & Sons Inc, 1971;, vol 20, pp 1-39.
30 +
Brooker G, Thomas LJ Jr, Appleman MM:  The assay of adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate in biological materials by enzymatic radioisotopic displacement . Biochemistry 7:4177-4181, 1968;.
31 +
Liddle GW, Hardman JG:  Cyclic adenosine monophosphate as a mediator of hormone action . New Eng J Med 285:560-566, 1971;.
32 +
Otten J, Johnson GS, Pastan I:  Cyclic AMP levels in fibroblasts: Relationship to growth rate and contact inhibition of growth . Biochem Biophys Res Comm 44:1192-1198, 1971;.
33 +
Gilman AG:  A protein binding assay for adenosine 3',5'-cyclic monophosphate . Proc Nat Acad Sci USA 67:305-312, 1970;.
34 +
Robison GA, Butcher RW, Sutherland EW:  Some actions of cyclic AMP , in Cyclic AMP . New York, Academic Press Inc, 1971;, chap 5, pp 128-136.
35 +
Heidrick ML, Ryan WL:  Adenosine 3',5' cyclic monophosphate and contact inhibition . Cancer Res 31:1313-1315, 1971;.
36 +
Masui H, Garren LD:  Inhibition of replication in functional mouse adrenal tumor cells by adrenocorticotropic hormone mediated by adenosine 3',5'-cyclic monophosphate . Proc Nat Acad Sei USA 68:3206-3210, 1971;.
37 +
Muneyama K, Bauer RJ, Shuman DA, et al:  Chemical synthesis and biological activity of eight-substituted adenosine 3',5'-cyclic monophosphate derivatives . Biochemistry 10:2390-2395, 1971;.

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