Pekka Autio

Systemic glucocorticoid treatment decreases serum concentrations of carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen

The effect of systemic glucocorticoid treatment on collagen synthesis in patients with various dermatoses was studied by measuring the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) in serum. Changes in the propeptide concentrations were compared with those of osteocalcin, which reflects osteoblastic activity, and tartrate resistant acid phosphatase (TRAP), which reflects osteoclastic activity. The treatment caused significant decreases in levels of PICP, PIIINP and osteocalcin of 38, 34 and 49%, respectively (P<0.001). For TRAP, both increases and decreases were seen. The effects on PICP and PIIINP were evident 2–4 days after the onset of steroid therapy. The decreases in PICP was dose‐related (r=0.470, P<0.005) but even relatively small doses (0.1 mg of prednisone/kg/1 day) caused a significant reduction in PICP. After cessation of treatment, the levels of PICP returned to the pretreatment level in 1 week. The present study demonstrates that systemic glucocorticoid therapy in humans suppresses the synthesis of type I and III collagens and also non‐collagenous bone matrix proteins.

Systemic glucocorticoids decrease the synthesis of type I and type III collagen in human skin in vivo, whereas isotretinoin treatment has little effect

The effects of systemic glucocorticoid and isotretinoin treatments on type I and type III collagen synthesis in intact skin were investigated by measuring the carboxyterminal and aminoterminal propeptides of type I procollagen, and the aminoterminal propeptide of type III procollagen, in suction blister fluid (SBF), in a study of 27 patients. All three parameters were significantly lower in the SBF of glucocorticoid‐treated patients than in controls or patients undergoing treatment with isotretinoin, whereas the latter two groups did not differ significantly from each other. During glucocorticoid treatment, the concentrations of the procollagen propeptides were only about 20% of the corresponding control values, indicating that systemic therapy with prednisone at a dose of 0.48 mg/kg per day almost totally abolishes collagen synthesis in the skin. These results indicate that systemic glucocorticoid treatment suppresses the synthesis of both type I and type III collagen in the dermis, and suggest that many side‐effects of these drugs, such as atrophy of the skin, are due to this inhibition. Systemic isotretinoin treatment did not stimulate skin collagen synthesis. Thus, its regenerative effect on connective tissue may be mediated by mechanisms other than direct stimulation of collagen synthesis.

Modulation of collagen synthesis and mRNA by continuous and intermittent use of topical hydrocortisone in human skin.

Background  Glucocorticoids have been shown to downregulate collagen synthesis in human skin in vivo, thereby contributing to skin atrophy.

Chronic UVB irradiation induces superoxide dismutase activity in human epidermis in vivo

In order to study the effects of repeated UVB exposures on the epidermal antioxidant defence system, we obtained epidermis samples from male volunteers who were exposed to chronic UVB irradiation. Chronic UVB irradiation was shown to be accompanied by induction of epidermal superoxide dismutase (SOD) activity in vivo, while the activities of the other antioxidant enzymes were not significantly changed. The repeated exposure of the epidermis to UVB irradiation was not accompanied by accumulation of products of lipid peroxidation reactions. As superoxide dismutase is of major importance in scavenging the reactive oxygen species, the UVB-induced changes in SOD activity might provide the epidermis a way of defending itself against the effects of chronic UVB irradiation.

Familial high serum PICP: high even in skin interstitial fluid, suppressible by topical corticosteroid treatment

Circulating C-terminal propeptide of type I procollagen (PICP), mostly originating from bone, is mainly cleared by mannose receptors (MRs) in liver endothelial cells (LECs). We hypothesized that skin macrophage MRs could also play a role in local (in situ) clearance of PICP originating from skin type I procollagen synthesis. We tested this hypothesis in a male subject with a genetic systemic clearance defect, apparently due to an abnormality in MR function in LECs (or in PICP structure). Since skin macrophages may express the same MRs as LECs do, the genetic defect could affect them as well; hence, if elevated PICP concentrations even in skin interstitial fluid (IF) were found in our subject, it would suggest a role for local MR-mediated PICP clearance in skin. Since glucocorticoids (GCs) upregulate MRs in vitro, we measured the effect of topical GC on suction blister fluid (SBF)-PICP of the test person as compared with normal subjects. SBF-PICP was elevated in the case, which was consistent with the hypothesis. Furthermore, the GC-induced decrease was accentuated. The results suggest that skin macrophage MRs can have a role in skin PICP clearance in situ.