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Notes: The quantitative changes in body hair growth, and sebaceous secretion, as well as plasma sex hormone binding globulin, luteinizing hormone and follicle stimulating hormone, testosterone and androstenedione were measured in a hirsute woman aged 21 years under ‘reverse sequential’ treatment with cyproterone acetate and ethinyl oestradiol. The subject, before treatment, had normal excretion of 17-oxosteroids, 17-oxogenic steroids, androsterone, dehydroepiandrosterone and aetiocholanolone.The rate of hair growth on the thigh and the average diameter of the hairs was significantly reduced after only 2 cycles of treatment. After 6–7 cycles the length attained by the terminal hairs was reduced and this appeared to be due mainly to change in growth rate rather than to alteration in the duration of anagen.The shorter and thinner hairs also had a much shorter region of pigniented medulla. A progressive decrease in the extent and continuity of the medulla could be detected after 3 cycles of treatment.Sebaceous secretion was also reduced after 2 cycles of treatment; and there was thereafter steady improvement of the pustular acne.Sex hormone binding globulin levels were low before treatment, unaltered by a first cycle of cyproterone acetate alone, but increased by addition of ethinyl oestradiol. Gonadotrophins remained low throughout, while testosterone and androstenedione levels, initially high, were substantially suppressed.

Notes: SUMMARY.— The pathogenesis of alopecia areata was studied by plucking hairs from each of a series of concentric zones, using felt patterns placed over lesions. It was possible to group lesions according to the zone with the greatest proportion of club hairs. The results are logically interpreted to mean that a wave of hair follicle damage or arrest moves centrifugally from a focal point beyond the area of alopecia.It is suggested that follicles may react in I of 3 ways. Firstly, severe damage may weaken the hair in the keratogenous zone, this being followed by breakage when the weak zone reaches the plane of the scalp; at the same time the follicle is precipitated into catagen and the hair is extruded as an exclamation mark. Secondly, the follicle may be precipitated into catagen with loss of the club in a normal manner, followed by replacement with a dystrophic anagen hair. Thirdly, the follicle may become dystrophic without a catagen phase.

Notes: Ageing and ultimate death, when survival offers no reproductive advantages to the species, are essential to the evolutionary process. Yet the prolongation of youth has always been a human dream. The prevention of ageing in visible areas of skin is desirable not for physiological but for social reasons; the skin proclaims our sexuality and asserts our social image. Has the aspiration any hope of success?Ageing of the skin involves changes in the dermis, epidermis, pigment cells, hair follicles, sebaceous and sweat glands, and sense organs. Some of these changes appear intrinsic to the organs concerned; some are dependent on hormonal and other systemic mechanisms; some involve environmental factors such as radiation. If changes of the first type appear to be inevitable, those of the second may be modifiable, and those of the third may, to some extent, be preventable. L'histoire physiologique du vieillissement de la peau

Notes: This study investigated the role of N-methyl-D-aspartate (NMDA)-type glutamatergic neurotransmission in mediating the photic induction of immediate-early gene expression in the Suprachiasmatic nucleus (SCN) of the Syrian hamster. Activation of c-fos, c-jun and egr-1 was assessed by immunocytochemical detection of their protein products. To characterize the circadian basis to the inductive effects of light, hamsters were allowed to free-run in constant dim red light and received a 1 h light pulse at different circadian phases relative to activity onset (defined as CT 12). In control animals which did not receive light pulses, c-fos and egr-1 expression was absent or restricted to a small area of the dorsolateral region of the SCN, and expression of c-jun could not be detected in the SCN. In hamsters killed after presentation of a light pulse at either CT 14 or CT 20, there was a marked increase in c-fos and egr-1 immunoreactivities throughout the ventrolateral division of the SCN. In contrast, light pulses given at CT4 or CT 8 failed to activate immediate-early gene expression. Light pulses did not induce c-jun immunoreactivity at any circadian phase tested. Staining for c-fos was maximal 1 h after the start of the light pulse and had started to decline by 2 h. At this later time, c-jun expression was still undetectable. To compare the distribution of retinal afferents with that of c-fos induction, hamsters held on a light schedule of 16 h light: 8 h dark received an intraocular injection of cholera toxin-horseradish peroxidase conjugate 3 days before exposure to a 1 h light pulse given 2 h after lights off. Comparison of adjacent sections processed for c-fos immunoreactivity or for cholera toxin-horseradish peroxidase revealed that light-induced c-fos expression was precisely restricted to retinal terminal fields in the SCN. Light pulses also induced c-fos expression in the retinoreceptive ventral lateral geniculate nucleus and intergeniculate leaflet but not in the retinal fields of the dorsal lateral geniculate nucleus, indicating that the expression of cfos in response to light is spatially specific.The aim of the subsequent experiments was to investigate the role of NMDA-type glutamatergic neurotransmission in mediating the effects of light on c-fos expression in the SCN. To determine whether NMDA had the potential to activate c-fos expression in the SCN, hamsters were infused with 2.5 nmol NMDA or vehicle via an intracerebroventricular (icv) cannula positioned adjacent to the nuclei. In contrast to the effects of light, icv NMDA activated c-fos expression at both CT8 and CT 14. The distribution of immunoreactivity was more widespread than that observed after light, extending throughout the SCN and adjacent hypothalamus. To test whether NMDA receptors had a physiological role in the photic response, hamsters were treated systemically with the non-competitive NMDA antagonist MK801 (dose range 0.6 to 6.0 mg/kg body wt, ip) or vehicle prior to exposure to a 1 h light pulse given at CT 14 or CT 20. Expression of c-fos was still detectable in the dorsolateral SCN but MK801 blocked expression in the ventral portion of the retinoreceptive zone of the SCN. MK801 (10 or 100 nmol) delivered centrally (icv) also prevented light-induced c-fos expression in the ventral region of the SCN bordering the optic chiasm, though staining again persisted in the dorsolateral region. The induction of c-fos by icv NMDA, and the partial blockade of light-induced c-fos expression by the antagonist MK801, are consistent with the hypothesis that glutamate mediates the effects of light on SCN activity. However, the persistent photic induction of c-fos expression in a subfield of retinal afferents following treatment with MK801 suggests that other, non-NMDA-type mechanisms may contribute to photic entrainment.

Notes: Photoperiodic control of the neuroendocrine axis is mediated by changes in the duration of the nocturnal melatonin signal. This study tested the hypothesis that reading of the signal depends upon the presence of a period free of melatonin between successive signals. Adult male Syrian hamsters were pinealectomized and received chronic subcutaneous infusions of melatonin or saline for 6 weeks. Animals which received saline had large testes. Those which received a single daily infusion which lasted for 10 h (50 ng/h) followed by 14 h without infusion underwent gonadal atrophy. Other animals received a compound melatonin signal in which the melatonin-free interval was occluded by a continuous infusion (25 ng/h). Superimposed upon this was a 10 h phasic increase in infusion rate such that the maximum rate of infusion was equivalent to that observed in controls (25 ng/h increase, 50 ng/h peak rate), or the increase in rate over the baseline was the same as in controls (50 ng/h increase, 75 ng/h peak rate). In neither group did the animals undergo gonadal regression. Analysis of iodomelatonin binding sites by in vitro autoradiography failed to reveal any systematic difference between animals which did and did not respond to melatonin and so the absence of a response could not be attributed to loss of receptors. These data demonstrate that the photoperiodic system cannot identify the melatonin signal solely upon the features of nocturnal peak height or amplitude of the peak over baseline. They are consistent with the hypothesis that the melatonin-free interval plays a significant role in photoperiodic time measurement.

Notes: The aim of this study was to investigate which characteristics of the nocturnal melatonin signal, in addition to its duration, convey photoperiodic information to the reproductive axis. To achieve control over the pattern of circulating melatonin, male Syrian hamsters held under stimulatory long daylengths (16h light:8h dark) were pinealectomized to remove the principal source of circulating endogenous hormone and then fitted with chronic subcutaneous cannulae through which programmed infusions of melatonin solution or vehicle could be delivered. Experiment 1 tested whether long intervals between successive melatonin signals impaired the photoperiodic response. Animals which received a short day-like melatonin infusion of 10 h duration once every 24 h (T = 24) for 6 weeks underwent gonadal atrophy. When the same number of signals (42) was delivered at a frequency of once every 32 h (T = 32), they were ineffective and animals remained gonadally active. Two infusion patterns were used to determine if the loss of response to 10 h signals given at T = 32 h was a consequence of the frequency per se or the long interval between signals (22 h). In the first, a ‘chimaeric’ signal which combined a long duration i.e. short day-like 18 h melatonin signal with a short day-like melatonin-free interval of 14 h (combined signal T = 32 h) was able to induce significant, but only partial, gonadal atrophy. Second, when the 22-h interval between 10-h melatonin signals was interrupted by a short (2 h) melatonin pulse, significant but partial gonadal regression again occurred. Moreover, the response depended upon the timing of the 2 h pulse. When this fell early in the melatonin-free interval, leaving a large portion of it intact, it had no effect on gonadal condition. In contrast, a pulse delivered in the middle of the interval, which divided it up into two short day-like segments of 10 h each, was partially effective in restoring a short day response. The second experiment tested whether melatonin signals delivered at a high frequency would induce a photoperiodic response. A 10 h infusion delivered once every 24 h caused gonadal atrophy. The same melatonin infusion delivered at a periodicity of 20 h (T = 20) was also very potent as a short day stimulus. However, when 10-h signals were delivered at the higher frequencies of once every 18 or 16 h, they were less effective. Only a minority of animals exhibited gonadal atrophy and overall the group means were not significantly different from those of saline-infused controls, but were significantly greater than those of the 24 and 20 h groups. These data demonstrate that the photoperiodic response to the melatonin signal is sensitive to the frequency at which the signal is received. However, there is no evidence for a circadian basis to this sensitivity, nor a dependence upon the relationship between the endocrine stimulus and the light-dark cycle, insofar as signals encountered at a non-circadian period of 20 h are very effective. Moreover, the effectiveness of signals encountered at longer periodicities can be modified by manipulation of the uninterrupted duration of the interval free of melatonin, demonstrating a role in photoperiodic time measurement for the duration of the interval between signals.

Notes: Cocaine and amphetamine-regulated transcript (CART) mRNA and immunoreactivity are expressed abundantly in the hypothalamus. Central administration of various fragments of this neuropeptide decreases food intake in rodents. To find out whether CART might play a role in the physiological regulation of energy balance, we used in situ hybridization to investigate whether CART mRNA abundance changed in two chronic obese/fat versus lean states and after acute dietary restriction. In the first study, mice were treated with goldthioglucose to destroy glucose-responsive neurones in the ventromedial hypothalamus. This produced hyperphagia and obesity: 7 weeks after treatment, those receiving goldthioglucose weighed 70% more than the controls. CART mRNA abundance in the arcuate nucleus of goldthioglucose-treated mice was decreased by 71% compared to levels in the control mice, but CART expression was unaffected in the dorsolateral hypothalamus. In the second study, male Siberian hamsters were exposed to short days to induce a physiological winter response in which body weight decreases as fat reserves are catabolized, and food intake correspondingly declines. After 8 weeks in short days, body weight had declined by 18% relative to controls maintained in long days in a summer fat state. CART mRNA levels did not differ significantly between the two groups in any hypothalamic areas. In the third study, male Siberian hamsters, either in long days or after 12 weeks exposure to short days to induce weight loss, were subject to a 48-h period of fasting. Although photoperiod per se did not affect CART expression, fasting produced a significant decrease in CART mRNA in the arcuate nucleus of hamsters in both the long- and short-day state. We conclude that CART-producing cells are involved in energy homeostasis: the marked decrease in CART expression in the arcuate nucleus in goldthioglucose-lesioned mice may contribute to the development of obesity, and the decrease following acute dietary restriction in hamsters may reflect a compensatory mechanism to reduce caloric expenditure, but our results do not indicate that CART is involved in long-term seasonal regulation of body weight.