Hair growth disorders cause significant psychological distress, but are poorly controlled. Since prostaglandin F₂α (PGF₂α) and prostamide F₂α analogue glaucoma treatments cause eyelash growth as side-effects, they may be useful for alopecia. How they function is unknown; possibilities include direct action on hair follicles or stimulating follicular blood flow. It is important to clarify whether scalp follicles can also respond as human follicle response to androgens differ with body site. Therefore, human scalp follicles were grown in vitro in organ culture with PGF₂α, latanoprost, a PGF₂α analogue, and bimatoprost, a prostamide F₂α analogue, with, or without, appropriate antagonists, and the presence of PGF₂α (FP) and prostamide F₂α receptors were investigated using molecular biological and immunohiostochemical methods. Each treatment significantly stimulated follicle growth rate, the percentage of growing follicles, and the amount of hair produced in a dose-responsive manner (10nM-1μM); the receptor antagonists blocked these effects. Immunohistochemistry of frozen scalp sections demonstrated FP protein only in dermal papillae and connective tissue sheaths. RT-PCR identified FP and various prostamide F₂α receptors in anagen follicles and isolated dermal papillae and bulbar connective tissue sheath, but not in bulb matrix or other epithelial tissues. Therefore, isolated human scalp hair follicles can respond biologically to PGF₂α and related pharmaceuticals in organ culture via follicular receptors and express the genes and protein for FP and prostamide F₂α receptors. PGF₂α-related drugs appear to act directly on follicles via receptors in the regulatory dermal papilla. They offer an exciting, novel approach for treating alopecia and merit clinical investigation.

Kurdistan Regional Government/Ministry of Higher Education and Scientific Research

No / The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F2¿ (PGF2¿)-sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC50=7.92±0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium-intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts. The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17-phenyl PGF2¿ (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1 ¿M bimatoprost on the mouse uterus. Analyses of the agonist¿agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17-phenyl PGF2¿. Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species-, tissue-, or preparation-related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost.