target for decades to regulate the estrus cycle as well as to induce labor in pregnant farm animals FP gene knockout in female mice blocks parturition. That is, these FP-/- mice fail to enter labor even if induced by oxytocin due to a failure in copus luteum regression and consequential failure to stop secreting progesterone (declining progesterone levels trigger labor). Studies with monkey and human tissues allow that FP receptors may have a similar function in humans. Skin pigmentation One side effect of applying FP receptor agonists to eyelashes in humans is the development of hyperpigmentation at nearby skin sites. Follow-up studies of this side effect indicated than human skin pigment-forming melanocyte cells express FP receptors and respond to FP receptor agonists by increasing their dendricites (projections to other cells) as well as to increase their tyrosinase activity. Since skin melanocytes use their dendrites to transfer the skin pigment melanin to skin keratinocytes thereby darkening skin and since tyrosinase is the rate-limiting enzyme in the synthesis of melanin, these studies suggest that FP receptor activation may be a useful means to increase skin pigmentation. Bone PGF2α triggers the NFATC2 pathway stimulating skeletal muscle cell growth. PGF2α, shown or presumed to operate by activating FP receptors, has complex effects on bone osteoclasts and osteoblasts to regulate Bone remodeling. However, further studies on the impact of the PGF2α-FP axis on bone are needed to better understand the pathophysiology underlying bone turnover and to identify this axis as a novel pharmacological target for the treatment of bone disorders and diseases. Inflammation and allergy Unlike other prostaglandin receptors which have been shown in numerous studies to contribute to inflammatory and allergic responses in animal models, there are few studies on the function of FP receptors in these responses. Gene knockout studies in mice clearly show that FP mediates the late phase (thromboxane receptor mediates the early phase) of the tachycardia response to the pro-inflammatory agent, lipopolysaccharide. PTGFR knockout mice also show a reduction in the development of pulmonary fibrosis normally caused by microbial invasion or bleomycin treatment. Finally, administration of PGF2α to mice causes an acute inflammatory response and elevated biosynthesis of PGF2α has been found in the tissues of patients with rheumatoid arthritis, psoriatic arthritis, and other forms of arthritis. While much further work is needed, these studies indicate that PGF2α-FP axis has some pro-inflammatory and anti-inflammatory effects in animals that may translate