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Effects of the Pineal Gland Upon the Hair Cycles in Mice

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Effects of the Pineal Gland Upon the Hair Cycles in Mice View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Tac JOURNAL OP INVESTIGATWE DRRMATOLOGT Vol. 47, No. 8 Copyright 1966 by The Williams & Wilkins Co. PrintedinU.S.A. EFFECTS OF THE PINEAL GLAND UPON THE HAIR CYCLES IN MICE ALBERTO B. HOUSSAY,5 M.D., JORGE H. PAZO,5 DD.S. AND CARLOS E. EPPER**, D.V.M. Hair growth in rats and mice is cyclic, each(17). Thus, the pineal gland has an effect both hair follicle having alternate periods of growthon the skin of amphibia and on some endocrine and rest. Also, the hair follicles develop inglands in mammals (16, 17, 18). The experi- waves of hair growth which cover gradually thements presented in this paper were performed to skin with a new coat of hair (1, 2, 3, 4, 5). ascertain its assumed role on the initiation and Diverse endocrine factors may be stimulantson the advance of hair growth waves in mice. or inhibitors, modifying the initiation, advance and characteristics of the hair wave (6, 7, 8, MATERIAL AND MEflIODS 9, 10). The inhibitory honnonal factors appear Male C8 H/Ep mice, approximately 3 months to be of pituitary origin, and its effect on theold, from the Animal Colony of the Comisión adrenals and gonads (6, 9, 10, 11). The stimu-Nacional de la EnergIa Atómica, Argentina, were lating hormonal factors are in part hypophysealused. The animals were fed on pellets of a common and in part extrahypophyseal (10, 11). Part oflaboratory diet (Forramez Lab, Molinos del Rio de la Plata, Buenos Aires, Argentina). Water was the stimulating action of the pituitary is pro-given ad libitum. duced by means of the thyroid (7, 8, 12, 13). Pinealectomy was performed in some groups of The nervous system also intervenes in theanimals using the technic of Pazo. A hole was regulation of the hair cycle. Slow hair wavesmade with a dental burr in the right parietal bone, were found in hemiarquidecortieated rats. Thisnear the back border, close to the midline. A 15 gauge needle was inserted through the hole and inhibitory effect is that of gonad stimulation,the pineal gland was removed by aspiration with a as shown by its suppression through castrationvacuum pump. The completeness of the operation (14). was checked when autopsy was performed. The Lesions of the olfactory cortex, especially thecontrol animals were sham-operated, following the anterior and internal part of the tuberculumsame procedure except that the suction was not applied and the pineal gland was not removed. olfactoriurn, resulted in slower pace of advance Radiothyroidectomy was performed with 100 of hair waves both in normal and in castratedmicrocuries of I 131 in some groups of animals, 60 mice (15). days before the pinealectomy or the sham opera- These data suggested the hypothesis of thetion. Castration was performed in some groups of thyroidectomized mice the day following the neurohormonal control of the hair growth wavespinealectomy or the sham operation. in rats and mice. Thus, mechanisms probably Melatonin was generously provided by Prof. A. located in the nervous system, would regularlyLerner, Yale University. It was dissolved in ab- alter the balance between the stimulating andsolute alcohol as to make a 5% stock solution. This material was added to saline for the injections. A inhibitory factors (15). daily dose of 100 micrograms was injected sub- The pineal gland is considered to be a neuro-cutaneously during 56 days. endocrine transducer and to regulate ovarian Every animal was clipped 7 days before pineal- function in mammals (16). Melatonin, activeectomy or the sham operation with an electric clipper number 0000, over an area extending along principle of the pineal gland, lightens the am-the back, from the neck to the base of the tail. phibian skin through its effect upon melanocytes The clipped area was observed twice a week throughout the experiment and the percentage of This investigation was partially supported bydenuded area covered by hair was estimated once the research grant N° 499 A on the "Neurohor-a week using the following method. The contours monal regulation of hair growth waves in rats and mice" from the Consejo Nacional de Investiga-of the denuded surfaces were drawn in a trans- ciones CientIficas y Técnicas, Argentina. parent paper of uniform width. The contours were Received for publication November 27, 1965. then cut out and these areas weighed in a Mettler * From the Department of Physiology, FacultyH 5 balance. The weight of the cuts, when the ani- of Dentistry, University of Buenos Aires, Argen-mal was clipped (0 day cuts), was compared with tina, and** From the Comisión Nacional de lathe other measurements in the same animal using EnergIa Atómica, Buenos Aires, Argentina. the following formula: 230 PINEAL GLAND AND HAIR CYCLES 231 Hair growth in denuded area (%) TABLE I of the cut X 100 Effects of Pinealectomy in Male C H Mice = 100—Weight Weight of the 0 day cut PinealectomizedSham-operated At the end of the experiments the animals wereAnimals killed with ether, and the adrenals, pituitary, thy- roid and testicles were carefully dissected and Number 8 9 25.0 0.724.4 0.7 weighed. Weight (g) The mean and standard error were calculated inOrgan weights(mg) every group of data and the probability was found Adrenals 3.2 0.2 3.4 0.1 using the "t" index of Fischer and Yates. Thyroid 2.5 0.1 1.9 0.03 Testicles 164.7 5.6145.3 2.2 RESULTS Pituitary 1.6 0.2 1.2 0.1 Effects of piriealectomy in normal mice.—In Experiment 1, the hair growth in the clipped areas was observed in 8 pinealectomized mice, Pinex Thyrex #Gonadex compared with 9 sham-operated controls. As it 5C ..Pinex#Thyrex is shown in Figure 1, a larger area was covered Thyrex'Gooadex / Thyrex / by hair in the pinealectomized mice than in the 4(ControIs / controls at the different intervals observed. After 53 days all the pinealectomized mice and none of the sham-operated controls had the clipped 1/ p area completely covered by hair. The average o area covered with hair in the sham-operated mice was 80.7%. /1 t7 The experiment was repeated several times and the clipped area was always covered with 0 7 21 35 49 hair more rapidly in the pinealectomized mice Days after pin ealectomy than in their sham-operated controls. Fia. 2. Effect of pinealectomy upon hair waves The animals in Experiment 1 were killed 53in thyroidectomized and castrated-thyroidecto- days after pinealectomy or the sham operation,mized mice. the weight of the organs being presented in Ta- Effects of pinealectomy in thyroidectomized ble I. There was a significant hypertrophy ofand in cast rated-t hyroidectomized mice.—In the thyroid (p < 0.001) and the testicles (p <Experiment 2, the hair growth was studied in the 0.01). No significant changes were found in the following 5 groups of mice: 1) castrated-thyroid- weight of pituitary and adrenals. ectomized-pinealectomized, 2) castrated-thyroid- ectomized-sham operated, 3) thyroidectomized- 0 pinealectomized, 4) thyroidectomized-sham 100 operated and 5) sham operated controls. The manner in which the clipped areas were 80 V covered by hair in the different groups is shown in Figure 2. The thyroidectomized mice were 60 very slowly covered by hair. A larger area was a) covered in control mice and a slightly larger one aL b 40 in castrated-thyroidectomized mice. In the two 0, groups in which pineal glands had been removed, //- - Pinealeclomy the area covered by hair was much larger than 20 — Controls in the other 3 groups, i.e., the pineal gland re- moval accelerated the hair wave in the castrated- 0'0 074 28 4253 thyroidectomized mice. The effect is more clearly days after piriea(ecfomy shown in the thyroidectomized mice where Fia. 1. Hair growth in pinealectomized andpinealectomy produced striking acceleration in sham-operated mice. the speed of the hair wave. 232 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY TABLE II Effect8 of Pinealecomy in Castraeed and Castrated-Thyroideclomized Mice Thyroidectomized Castrated-thyroidectomized Controls Sham-operation Pinealectomy Sham-operation Pinealectomy Sham-operation Animals Number 13 8 12 6 6 Weight (g) 24.0 0.6 24.0 0.8 23.4 0.5 23.0 1.0 26.7 0.7 Organ weights (mg) Adrenals 5.7 0.1 6.0 0.4 5.7 0.1 6.0 0.1 5.4 0.4 Thyroid — — — — 2.8 0.2 Testicles 171.5 3.7 173.3 5.0 — — 150.9 6.4 10c 'f hair more slowly in the melatonin injected mice, either pinealectomized or sham-operated. at: The weight of the organs is shown in Table III. There is thyroid hypertrophy (p <0.05) in pinealectomized mice. The administration of 6c I-0 melatonin decreased thyroid weight in pinealec- L /,:::v tomized mice (p < 0.02) but not in the sham- 4C f7 operated mice. Melatonin increased adrenal j? ._.Piriealectomiz& weight in the sham-operated mice (p <0.001) but not in the pinealectomized mice. 2C -tr%°''° DISCUSSION o 12 24 36 48 The results presented in this paper indicate Days cf/er pinealectomy that the hair growth waves run faster in pineal- Fic. 3. Effects of daily administration of 100 egectomized C,H/Ep mice than in their sham- of melatonin during 56 days in pinealectomizedoperated controls. This effect could be direct and sham operated mice. upon the skin or mediated through some endo- crine alteration. If the thyroid hypertrophy The weight of the endocrine organs in thesefound in the autopsy study indicated thyroid groups of animals is shown in Table II.
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