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A. HOWE and A. J. THODY

SUMMARY

The changes in the content of melanocyte-stimulating hormone (MSH) and histology of the neuro-intermediate (n.i.) lobe were followed in rats which drank 2% sodium chloride for periods from 1–15 days.

The pars intermedia showed a biphasic response. During the initial phase of 1–4 days there was a rapid rise in the MSH content, by 153% in the first day, falling back to control level by 4 days. These fluctuations were paralleled by an increase in the normally small numbers of Type 2 cells and at the same time numerous Type I cells showed hypertrophy and degranulation.

After 4 days on saline there was a second rise in the MSH content, which was still evident at 15 days; during this second period the number of Type 2 cells declined to normal levels. The degranulated Type 1 cells also disappeared, most of Type 1 being smaller in size and intensely PAS-positive.

After the ingestion of saline it apparently takes several days before the pars intermedia adapts to a new level of activity.

The likely significance of these changes and the possibility of a relationship between the pars intermedia and the neurohypophysis are discussed.

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A. HOWE and A. J. THODY

SUMMARY

The adenohypophysis of the pig was examined histochemically for the presence of 11 oxidative enzymes, namely: 1.1.1.27 l-lactate: NAD oxidoreductase, 1.1.1.30 d-3-hydroxybutyrate: NAD oxidoreductase, 1.1.1.37 l-malate: NAD oxidoreductase, 1.1.1.41 threo-d s-isocitrate: NAD oxidoreductase (decarboxylating), 1.1.1.42 threo-d s-isocitrate: NADP oxidoreductase (decarboxylating), 1.1.1.49 d-glucose-6-phosphate: NADP oxidoreductase, 1.1.99.5 l-glycerol-3-phosphate: (acceptor) oxidoreductase, 1.3.99.1 succinate: (acceptor) oxidoreductase, 1.4.1.2 l-glutamate: NAD oxidoreductase (deaminating), 1.6.99.1 reduced-NADP: (acceptor) oxidoreductase, 1.6.99.3 reduced-NAD: (acceptor) oxidoreductase.

With the exception of 1.1.1.30 d-3-hydroxybutyrate: NAD oxidoreductase, activity was found throughout the adenohypophysis for all these enzymes. A comparison was made with the activity for these enzymes in liver.

In the adenohypophysis, the pars tuberalis exhibited the highest activity for all enzymes, generally equal to or greater than that shown by the liver. The pars intermedia and the pars anterior showed similar activity for these enzymes, in general of a lower order than that given by the liver. The pattern of enzyme distribution in the pars intermedia is described; high activity for 1.1.1.37 l-malate: NAD oxidoreductase, 1.1.1.27 l-lactate: NAD oxidoreductase, 1.6.99.3 reduced-NAD: (acceptor) oxidoreductase, 1.6.99.1 reduced-NADP: (acceptor) oxidoreductase was shown by cells lining cysts and the pituitary cleft.

The findings are discussed in relation to the possible association of these enzymes with secretory function.

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G HUNT and A J THODY

Abstract

In animals, the coat-darkening effects of α-melanocyte stimulating hormone (α-MSH) are opposed by agouti protein. Although agouti protein has been shown to be a competitive antagonist of the melanocyte-associated MC-1 melanocortin receptor, the possibility that agouti protein can affect melanogenesis independently of its ability to antagonise melanocortin activity cannot be excluded. This study demonstrates that murine agouti protein causes both a time- and concentration-dependent suppression of melanogenesis in B16 F1 murine melanoma cells. In addition, human agouti protein decreases melanogenesis in cultured human epidermal melanocytes. However, agouti protein has little effect on the ability of α-MSH to stimulate melanogenesis. These observations raise fundamental questions about the mode of action of agouti protein in regulating melanogenesis.

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A. J. THODY and S. SHUSTER

SUMMARY

Thyroidectomy of intact and castrated rats produced significant reductions in their rates of sebum secretion. Replacement therapy with thyroxine (T4) increased the rate of sebum secretion of the castrated-thyroidectomized rats. Treatment with testosterone propionate also stimulated sebum secretion in castrated-thyroidectomized rats. When given together these two hormones had an additive effect on the rate of sebum secretion.

Thyrotrophic hormone (TSH) stimulated sebum secretion in castrated-hypophysectomized, but not in thyroidectomized rats.

It is concluded that TSH affects sebum secretion through its action on the thyroid, presumably by stimulation of T4 secretion.

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A. J. THODY and S. SHUSTER

SUMMARY

The effect of varying doses of testosterone propionate (TP) on the sebum secretion and preputial gland weight of castrated and hypophysectomized—castrated rats was studied. The changes in preputial gland weight closely paralleled those of sebum secretion. Small doses of TP (0·05 mg) stimulated sebum secretion in hypophysectomized-castrated rats, but not in the castrated rats. Higher doses of TP increased sebum secretion in both the hypophysectomized—castrates and the castrated rats.

While 0·5 mg TP completely restored sebum secretion to normal levels in castrated rats but not in the hypophysectomized—castrated rats, the actual increase in sebum secretion produced by this dose of TP was similar in both groups. It is concluded that at physiological doses the action of TP on the sebaceous glands is independent of the pituitary. However, the presence of the pituitary is required for normal sebaceous gland activity.

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A. J. THODY and S. SHUSTER

SUMMARY

The effect of α-MSH on sebum secretion and preputial gland weight was examined in intact, castrated and hypophysectomized male rats and in hypophysectomized rats receiving treatment with either testosterone propionate (TP) or progesterone. After treatment with α-MSHMSH for 2 weeks, increases in sebum secretion occurred in intact, castrated and hypophysectomized rats, but larger responses were found in the hypophysectomized rats that had received treatment with either TP or progesterone, suggesting that α-MSH acts synergistically with TP and progesterone to stimulate sebum secretion. α-Melanocyte-stimulating hormone also increased preputial gland weight in intact rats, but there was no response after castration and only a small response after hypophysectomy. However, when the hypophysectomized rats received simultaneous treatment with either TP or progesterone, α-MSH increased preputial gland weight.

It is suggested that α-MSH acts directly on the sebaceous glands to stimulate lipogenesis and, together with steroid hormones, may have an important role in controlling sebaceous gland function in the rat and other hairy mammals. With the evolution of hair, certain of the MSH peptides may have lost their significance as pigmentary hormones and have developed a sebotrophic function. For this reason, it might be more appropriate to refer to these peptides as the 'sebotrophins'.

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A. J. THODY and S. SHUSTER

SUMMARY

Adult male rats which had been castrated prepuberally secreted less sebum than intact rats. When hypophysectomy followed castration there was a further decrease in sebum secretion. Treatment of the castrated and hypophysectomized castrated rats with testosterone propionate produced a large and comparable increase in the sebum secretion of both groups. Testosterone propionate also caused a marked increase in the preputial gland weight of the castrated rats, although a much smaller response occurred after hypophysectomy. The effect of hypophysectomy on the response of the sebaceous and preputial glands to testosterone is discussed.

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A. J. THODY and S. SHUSTER

Department of Dermatology, University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 4LP

(Received 15 October 1976)

In 1972 we suggested that α-melanocyte-stimulating hormone (α-MSH) had a physiological role as a sebotrophic hormone in the rat (Thody & Shuster, 1972) and it now appears that α-MSH is the previously suspected but unidentified sebotrophic hormone (Thody & Shuster, 1973; Shuster & Thody, 1974).

Since previous studies have mainly been concerned with exogenous MSH we examined the effect on sebum secretion of changes in endogenous MSH secretion induced by drugs.

Adult Wistar rats were housed in a light and temperature-controlled room and maintained on tap water and Oxoid breeding diet. The following treatments were carried out for 2 weeks after which time sebum secretion was measured by the method of Archibald & Shuster (1970). (i) Trifluoperazine (Smith, Kline & French) (0·5 mg/day) was administered intraperitoneally in 0·9% saline to male rats twice

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A. J. THODY and S. SHUSTER

SUMMARY

Testosterone propionate (TP) was administered to female rats at 3 and 6 days of age. When adult the sebum secretion rate of these rats was significantly increased, although the response to TP was normal.

Neonatal androgen treatment had no effect on the preputial gland weight of adult female rats. On the other hand ovarian weight was reduced.

After ovariectomy of normal adult rats there was an increase in sebum secretion to a level comparable to that found in adult rats given TP as neonates. By contrast there was no change in sebum secretion after ovariectomy of adult rats given TP as neonates and the rate of sebum secretion in these rats was comparable to that in ovariectomized normal adults.

It is suggested that after neonatal androgen treatment the normal inhibition of the sebaceous glands by the ovaries was abolished and consequently the rate of secretion was increased. Thus the endocrine state in early life may have a lasting effect on sebaceous gland activity in the adult.

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A. J. THODY and S. SHUSTER

It is generally believed that the activity of the sebaceous glands depends to a large extent on the gonads. The pituitary also appears to be involved in the physiology of these glands (Ebling, Ebling & Skinner, 1969; Nikkari & Valavaara, 1969; Thody & Shuster, 1970). The relationship between the pituitary and the sebaceous glands may be exerted via growth hormone and prolactin for Ebling et al. (1969) have shown that these pituitary hormones facilitate the effect of testosterone on sebum secretion. This present study was carried out to see whether the pituitary influence on sebum secretion is also mediated through the thyroid and adrenal glands.

The rate of sebum secretion was measured (Archibald & Shuster, 1969) in 12- to 15-week-old rats which had received one of the following treatments: castration, castration and adrenalectomy, castration and thyroidectomy, castration and hypophysectomy, or no treatment (intact controls). Castration was carried out when the