P6.60 EFFECTS OF PROLACTIN ON MURINE HAIR CYCLES ARE MEDIATED DIRECTLY WITHIN THE SKIN

Allan J Nixon¹, Christopher J Ormandy², Murray G Ashby¹, Katrina Blazek², Allan J Pearson¹

¹AgResearch, Hamilton, New Zealand.  ²Garvan Institute of Medical Research, Sydney, NSW Australia.

The advance of hair growth cycles observed in prolactin receptor (PRLR) knockout mice has demon­strated that prolactin signalling can influence the inherent timing mechanism of hair growth.  However, whether this is a direct action of prolactin on the skin or medi­ated indirectly, e.g. through other hormones, remains unclear.  The aim of this study was therefore to test prolactin’s mode of action by determining hair cycle times in PRLR knockout skin maintained on host animals that restore normal endocrine function in other tissues.

Skin explants (2x5 mm) from 23 day old homozygous PRLR null and wildtype litter­mates were grafted onto 5-6 week old NOD-SCID mice of the same sex.  Ten host mice each carried two grafts on their scapular regions, one graft of each donor genotype.  Contrasting coat colours of donor and host facilitated the monitoring of hair growth, using skin pigment­ation and emergent fibre length to define subsequent growth cycles.  In addition, skin homografts using wildtype and PRLR null mice were performed as controls for the effects of surgery.

The grafts exhibited three periods of growth over 14 weeks following grafting, interspersed with longer periods of quiescence.  These did not precisely correspond to hair cycles in either hosts or ungrafted skin of knockout and wildtype mice.  However, hair cycles within knockout grafts, which lack a functional PRLR protein, generally preceded those of wildtype grafts, which have normal signalling capability.  For example, the second cycle after surgery was advanced in PRLR null grafts by 6.8 ± 3.2 days (P<0.05) and 9.1 ± 2.7 days (P<0.005) (mean difference ± SED) for males and females respectively.

These results extend the evidence that prolactin can inhibit hair growth in mammals with both seasonal and non-seasonal cycles.  They demonstrate that at least part of this effect is attributable to the direct action of prolactin within the skin, signalling via receptors which have been localised in hair follicles.  Dissecting local and systemic contributions in the mouse knockout model in this manner is potentially useful for interpreting the presently ambiguous hormonal influences in human hair-related conditions such as hyperprolactinemia and telogen effluvium.