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V. A. Randall, M. J. Thornton and A. G. Messenger

ABSTRACT

Androgens stimulate hair growth in many areas, e.g. the beard; they also induce regression and balding on the scalp with increasing age in genetically disposed individuals. The cause(s) of this biological conundrum is unknown but age-related; androgen-potentiated changes also occur in the prostate. The mesenchymederived dermal papilla situated at the base of the hair follicle is thought to play an important role in regulating the growth and development of the follicular epithelium. Since androgens probably act on the hair follicle via the dermal papilla, cultures of dermal papilla cells from human hair follicles with differing responses to androgens in vivo have been established and their ability to bind androgens assessed. Receptor binding was assayed by saturation analysis (0·05–10 nmol/l) using the synthetic non-metabolizable androgen, [3H]mibolerone. Shionogi 115 cells were also assayed as a positive control.

Specific high-affinity low-capacity androgen receptors were identified in 12 dermal papilla primary cell lines with similar characteristics to established androgen receptors. Cells from androgen-sensitive follicles (beard, scrotum and pubis) contained higher levels of androgen receptors than those derived from relatively androgeninsensitive non-balding scalp follicles whether the receptor content was calculated in relation to cell number, protein or DNA content of the cells. These results support the hypothesis that androgens act on hair follicles via the dermal papilla in vivo and demonstrate that dermal papilla cells exhibit an altered phenotype in culture which depends on the body site from which they were derived. Cultured human dermal papilla cells should prove a useful model system for studies of the mechanism of androgen action, and further investigations may elucidate the paradox of why bald men can grow beards.

Journal of Endocrinology (1992) 133, 141–147

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J. A. Charlton, C. J. Thompson, J. M. Palmer, S. Thornton and P. H. Baylis

ABSTRACT

To investigate whether hyperglycaemic ketoacidotic diabetic rats continue to osmoregulate the secretion of arginine vasopressin (AVP), male Wistar rats were injected with streptozotocin (150 mg/kg body weight). Rats rendered diabetic were maintained on protamine–zinc insulin (PZI) for 11 days (insulin-treated rats; n = 35), after which PZI was withdrawn for 72 h in half the rats (insulin-withdrawn rats). Insulin-withdrawn and -treated rats were divided into two groups; one was injected i.p. with distilled water (20 ml/kg) and the other with hypertonic saline (500 mmol NaCl/l; 20 ml/kg), and killed 30 min after injection. Insulin-withdrawn rats (water loaded and osmotically stimulated) were hyperglycaemic (16·5 ± 0·8 and 16·5 ± 0·9 mmol glucose/l respectively) and ketotic (2077 ± 664 and 1474 ± 170 μmol acetoacetate/l respectively). Insulin-treated rats were euglycaemic and non-ketotic. Osmotic manipulation caused similar changes in plasma sodium in both insulin-withdrawn and -treated rats. Plasma AVP was low in the water-loaded rats (0·6 ± 0·1 and 4·5 ± 0·9 pmol/l in the insulin-treated and -withdrawn rats respectively) and increased in rats injected with hypertonic saline (1·2 ± 1·8 and 35·2 ± 17·9 pmol/l respectively). There was no evidence of hypotension and hypovolaemia in any group of rats. Linear regression analysis defined the functions: plasma AVP = 2·56 (plasma Na – 141), r = +0·63, P < 0·01 for hyperglycaemic ketotic rats; plasma AVP = 0·83 (plasma Na – 146), r = +0·78, P < 0·001 for insulin-treated animals. The slopes and abscissal intercepts were significantly (P < 0·05) different. We conclude that the hyperglycaemic ketotic diabetic rat retains the ability to osmoregulate AVP secretion.

Journal of Endocrinology (1989) 123, 413–419

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M S Fernandes, V Pierron, D Michalovich, S Astle, S Thornton, H Peltoketo, E W-F Lam, B Gellersen, I Huhtaniemi, J Allen and J J Brosens

Rapid non-genomic actions of progesterone are implicated in many aspects of female reproduction. Recently, three human homologues of the fish membrane progestin receptor (mPR) have been identified. We combined bioinformatic analysis with expression profiling to define further the role of these mPRs in human reproductive tissues. Sequence analysis confirmed that the mPRs belong to a larger, highly conserved family of proteins, termed ‘progestin and adiponectin receptors’ (PAQRs). A comparison of the expression of mPR transcripts with that of two related PAQR family members, PAQRIII and PAQRIX, in cycling endometrium and pregnancy tissues revealed markedly divergent expression levels and profiles. For instance, endometrial expression of mPRα and γ and PAQRIX was cycle-dependent whereas the onset of parturition was associated with a marked reduction in myometrial mPRα and β transcripts. Interestingly, mPRα and PAQRIX were most highly expressed in the placenta, and the tissue expression levels of both genes correlated inversely with that of the nuclear PR. Phylogenetic analysis demonstrated that PAQRIX belongs to the mPR subgroup of proteins. We also validated a polyclonal antibody raised against the carboxy-terminus of human mPRα. Immunohistochemical analysis demonstrated more intense immunoreactivity in placental syncytiotrophoblasts than in endometrial glands or stroma. The data suggest important functional roles for mPRα, and possibly PAQRIX, in specific reproductive tissues, particularly those that express low levels of nuclear PR.