011 Prolactin Receptor Knockout Mice Have Altered Hair Growth Cycles

A.J. Craven1,2, C.J. Ormandy3, A.J. Nixon1, P.A. Kelly4, R.J. Wilkins2, A.J. Pearson1 1AgResearch, Ruakura Research Centre, Hamilton, New Zealand. 2University of Waikato, Hamilton, NZ. 3Garvan Institute of Medical Research, Sydney, Australia. 4INSERM Unité 344, Paris, France.

Although prolactin has been shown to entrain hair growth cycles in seasonally responsive mammals, no comparable role has been identified in the age-dependent pelage replacement of rodents. We therefore analysed hair growth cycles in prolactin receptor gene-disrupted mice (PRLR-/-) to determine the influence of prolactin signaling on murine hair cycles. The second (G2) hair cycle of PRLR-/- mice on the 129SV background, and their wildtype (PRLR+/+) and heterozygote (PRLR+/-) littermates, were visualized and compared by dyeing their coats at 28 days postpartum and observing the emergence of undyed fur. Samples of mature pelage were collected for measurement of fibre length and diameter distribution. The growth development status of hair follicles in adult and neonatal mice was determined by skin histology. The expression of PRLR in the skin was detected by RT-PCR and immunocytochemistry. The hair growth phenotype of PRLR-/- mice consisted of a change in the timing of hair cycling events. Although no hair follicle development differences were noted in PRLR-/- neonates, G2 hair replacement in PRLR-/- mice occurred earlier than in wildtypes. In female PRLR-/- mice, fibres erupted on the dorsum by 33.0 ± 0.7 days of age in mice in contrast to 61.9 ± 2.8 days in PRLR+/+ mice (P<0.001). PRLR+/- mice were intermediate (50.1 ± 3.2 days). In males, a similar effect, but with a much reduced difference between the PRLR-/- and PRLR+/+ genotypes was observed (31.0 ± 1.0, and 34.9 ± 0.7 days respectively; P<0.001). Thus PRLR deficiency eliminated the sexual dimorphism associated with murine hair replacement. Once initiated, the pattern and progression of hair replacement across the body was similar in all genotypes. All fibre types were present and appeared structurally normal, but PRLR-/- mice had slightly longer (P<0.001), and coarser (P<0.05) hair than wildtypes. mRNA encoding both the long and short-3 forms of prolactin receptor were found in the skin of both adult and neonate wildtype mice. The receptor protein was immunolocalized to the outer root sheath of the hair follicle as well as the epidermis, sweat and sebaceous glands. These findings suggest that prolactin has an inhibitory effect on murine hair cycle events.