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The relative responses to testosterone of the prostate, preputial, Harderian, and lachrymal glands, the seminal vesicles and the brown adipose tissue, have been compared in litter-mate, castrated and hypophysectomized–castrated rats, with or without treatment with bovine GH. The responses of both prostate and preputial glands, though not the seminal vesicles, were reduced by hypophysectomy, and restored by GH. Growth hormone had some independent action on the preputial glands, but most of its effect was synergistic with testosterone. The response of brown adipose tissue to testosterone was similarly reduced by hypophysectomy, but was not restored by the GH. The weights of the Harderian and lachrymal glands were not affected by castration, but they were considerably reduced by hypophysectomy. Growth hormone had a slight restorative effect on the Harderian glands, but none on the lachrymal glands.

Summary.Reproductive responses to photoperiod were directly compared in mature ewes and in their spring-born twin female lambs. All females were ovariectomized and treated with oestradiol implants before transfer into artificial photoperiod; serum LH concentrations and pulsatile LH patterns provided an index of neuroendocrine reproductive activity. Mothers were transferred from natural photoperiod to artificial long days (16 h light:8 h dark) at the summer solstice so that no decrease in photoperiod would be experienced. These ewes began reproductive activity synchronously at the expected time in the autumn. One of each pair of twin lambs was treated exactly as the mothers; to determine the normal timing of puberty the remaining twin was maintained in a photoperiod simulating the natural decrease in daylength. In all 6 control lambs experiencing the simulated natural photoperiod, reproductive activity occurred synchronously at 28 ± 1 weeks of age (2 October ± 7 days). However, in their twin sisters which did not experience a decrease in photoperiod, only 2 of 6 lambs had begun reproductive activity by the end of the experiment at 52 weeks of age (March), and these were both delayed relative to their twin control lambs exposed to decreasing daylength. Therefore, a decrease in photoperiod is necessary for the normal timing of puberty in the spring-born, female sheep, whereas seasonally anoestrous, mature sheep can enter the breeding season at a normal time in the absence of decreasing photoperiod. We suggest that the requirement for a decreasing photoperiod by the spring-born lamb reflects its limited photoperiodic history as compared to the adult.Keywords:puberty; photoperiod; sheep; LH

Soay rams were treated with naloxone and/or morphine at different stages of their annual reproductive cycle to study the role of endogenous opioid peptides in the control of pulsatile LH secretion. The responses in intact rams were compared with those shown by pinealectomized (PNX) or superior cervical ganglionectomized (SCGX) rams which had a different annual testicular cycle. Naloxone (4–6 mg/kg i.v.) given to intact rams at four times of the year induced significant increases in LH pulse frequency in the breeding season in September and December, but minimal responses in the non-breeding season in June. Similar treatments given to PNX or SCGX rams induced good responses in March, June and September and the poorest response in December; the different seasonal pattern between the intact and PNX/SCGX rams was correlated with differences in the timing of their testicular cycles.Morphine (1 mg/kg i.v.) induced a significant decrease in LH pulse frequency when given to intact rams in October, but no significant effects were observed when morphine was given to sexually inactive rams in early July. Naloxone (1 mg/kg i.v.) given concurrently with morphine in October reversed the suppressive effect and resulted in an actual increase in LH pulse frequency above pretreatment levels. Morphine-treated rams showed normal LH responses to injections of LH-releasing hormone (LHRH) indicating that the site of opiate inhibition was on hypothalamic LHRH secretion rather than on pituitary LH release.Chronic treatment of intact and PNX rams with naloxone 1 mg/kg every 4 h for 7 days) in April and October produced the expected acute increase in LH pulse frequency in the intact rams in October, and at both times of year in the PNX rams, however there was no sustained increase in LH secretion in response to chronic naloxone in any of the treatment groups. The response to the second naloxone injection was much reduced and was absent after 3 days; responsiveness to naloxone was restored within 2 days of stopping the chronic treatment.The overall results indicate that an endogenous opioid mechanism is involved in the tonic inhibition of LH secretion and that this mechanism is most active in the breeding season when both naloxone and morphine have marked effects on pulsatile release of LH. Regulation of endogenous opioids in the hypothalamus may be part of the mechanism by which environmental factors modulate steroid negative-feedback control of LHRH and thus LH secretion in seasonally breeding mammals.J. Endocr.(1985) 107,341–353

The uptake and metabolism of radioactively labelled testosterone was investigated in vivoat various time intervals in the skin, plasma and other tissues of adult rats castrated 24 h earlier. After the addition of marker steroids the components of the tissue extracts were separated by partition and development in several chromatographic systems; steroid identification was confirmed by derivative formation and recrystallization to constant 3H:14C ratio.The skin resembled the classical androgen target organs in the uptake and retention of both total and unconjugated radioactivity, but the actual composition of the radioactivity present in the skin was markedly different from that in the accessory glands. Little testosterone was recovered from the ventral prostates and 5α-dihydrotestosterone (5α-DHT), often considered the active intracellular androgenic steroid, constantly occupied the largest proportion of the extracted radioactivity. In the skin samples, however, testosterone was always the major unconjugated steroid detected and 4-androstene-3,17-dione, 5α-DHT, 5α-androstane-3α,17β-diol, androsterone and 5α-androstane-3β,17β-diol were only identified in much smaller quantities, even after 5 h. Although the majority of the plasma radioactivity was conjugated or very polar by 20 min, all the steroids found in the skin were present, albeit in different proportions; testosterone was always predominant and 5α-androstane-3β,17β-diol was also detected in larger amounts than the very low levels of the other steroids.The results suggest that 5α-DHT is not as important in the skin as it is in the prostate of the rat and that other androgenic steroids, most notably testosterone itself, may be involved in the mechanism of androgen action in the skin.

Summary.Seasonal cycles in the size of the testes, blood plasma concentration of testosterone, FSH and prolactin, intensity of the sexual skin flush, timing of rutting behaviour and moulting of the body coat were recorded in Soay rams after s.c. implantation of melatonin contained in a Silastic envelope which increased the circulating blood levels of melatonin to 200–600 pg/ml for many months. Two groups of 8 adult rams were held under alternating periods of short days (8L:16D) and long days (16L: 8D) to drive the seasonal cycles and the treatments with melatonin were initiated during the long or short days, and one group of 8 ram lambs was kept out of doors and given implants during the long days of summer (4 melatonin-implanted and 4 control (empty implants) rams per group).The treatments demonstrated that (1) melatonin implants during exposure to long days resulted in a rapid 'switch on' of reproductive redevelopment similar to that produced by exposure to short days; (2) melatonin implants prevented the rams from showing the normal responses to changes in the prevailing photoperiod rendering them non-photoperiodic; and (3) long-term cyclic changes in testicular activity, prolactin secretion and other characteristics occurred in the melatonin-implanted rams; the pattern was similar to that previously observed in rams exposed to prolonged periods of short days.The overall results are consistent with the view that melatonin is the physiological hormone that relays the effects of changing photoperiod on reproduction and other seasonal features, and that continuous exogenous melatonin from an implant interferes with the normal 'signal' and produces an over-riding short-day response.

α-Melanocyte-stimulating hormone was shown to act synergistically with testosterone to stimulate the sebaceous, prostate and preputial glands and the seminal vesicles in hypophysectomized-castrated rats. The sebaceous glands differed from the other three organs in that α-MSH not only acted synergistically, but also had a significant effect which was independent of the presence of exogenous testosterone. The response of the brown adipose tissue to testosterone, considerably reduced by hypophysectomy, was not restored by α-MSH. The Harderian and lachrymal glands were also pituitary-dependent and their weights in hypophysectomized-castrated rats were not restored by α-MSH.

Circulating prolactin concentrations were monitored during the early postnatal period in sheep to evaluate their response to photoperiod. In the first experiment, male and female lambs were exposed from 1 week of age, with their mothers, to either long days (16 h light:8 h darkness; n= 15) or short days (8 h light:16 h darkness; n= 16) to test whether they could discriminate different day lengths. In both sexes, serum prolactin concentrations were higher on long than on short days during the first 7 weeks after birth. In the second experiment, female lambs (n= 21) were raised on long days from 2 weeks of age. The superior cervical ganglia were removed bilaterally at 4 weeks of age from 14 lambs to lesion the sympathetic innervation to the pineal gland, and thus ablate the nocturnal increase in pineal melatonin secretion. After surgery, serum prolactin concentrations on long days were significantly lower in ganglionectomized lambs than in the intact controls. In the third experiment, the amplitude of the night-time melatonin rise was artificially increased in female lambs (n= 8) between 2 and 7 weeks of age to adult levels. Unrestrained lambs were infused during the 8-h dark phase of each day with melatonin by means of a self-contained, computerized syringe-pump. Concentrations of circulating prolactin did not differ from those in uninfused lambs (n= 8) with lower endogenous nocturnal melatonin. These results reveal that the sheep can discriminate photoperiod cues during the early postnatal period, and suggest that the low-amplitude melatonin rhythm in the neonatal lamb is sufficient to mediate this response.J. Endocr. (1988) 119,211–218

The role of endogenous opioid peptides in the inhibitory control of pulsatile LH secretion was studied in adult Soay rams at different stages of the seasonal reproductive cycle, entrained by an artificial lighting regimen of alternating 16-week periods of long and short days. The LH responses to the acute administration of naloxone (opioid antagonist) and morphine (opioid agonist) were measured in intact rams (n= 7), testosterone-implanted castrated rams (n= 8) and castrated rams (n= 8) to assess the interaction between photoperiod and gonadal steroids in the opioid control of LH secretion.In the intact and testosterone-implanted castrated rams, naloxone (1·7 mg/kg i.v.) increased and morphine (1·0 mg/kg i.v.) decreased mean LH concentrations and LH pulse frequency during the sexually active phase under short days, but these effects were reduced or absent during the inactive phase under long days. The changes in the LH responses occurred in close parallel with the photoinduced changes in endogenous LH secretion. In the castrated rams receiving no supplementary testosterone, plasma LH concentrations were permanently raised and there were only minor changes related to the photoperiod. Naloxone (1·7 mg/kg) induced transient increases in LH secretion at all stages, and morphine (1·0 mg/kg) failed to suppress LH levels under both short and long days. LHRH stimulation tests revealed that there were changes in LH release related to the induced reproductive cycle in the intact and testosterone-implanted rams but not in the castrated rams; these changes in the responsiveness of the pituitary gonadotrophs to LHRH could not account for the changes in the LH response to the opiate drugs.These results illustrate that an endogenous opioid mechanism is involved in the tonic inhibition of LH secretion acting to regulate the pulsatile release of LHRH from the hypothalamus. This system can be shown to be functional in a steroid-dependent manner in the sexually active phase of the seasonal cycle, but not in the inactive phase of the cycle when non-opioidergic mechanisms are presumed to predominate in the inhibition of LH secretion.J. Endocr.(1987) 115,425–438

1. In the dorsal skin of female albino rats, the sebaceous glands reached their maximum size, and the stratum germinativum its greatest thickness during prooestrus. At oestrus, and on the day following it, both these tissues were significantly reduced in size.2. During the oestrous cycle, there appeared to be no significant changes in the incidence of mitoses in either tissue, as measured 5 hr after injection of colchicine.3. An analysis of correlation showed that in neither tissue was size correlated with incidence of mitoses. Sebaceous gland size was very significantly correlated with epidermal thickness, and the two incidences of mitoses were themselves correlated.4. In immature female rats, which had been implanted with oestradiol benzoate 3–4 weeks before death, both sebaceous gland size and epidermal thickness were greatly reduced, although the incidences of mitoses were significantly raised.5. These results are interpreted as indicating that oestrogens affect both holocrine secretion of the sebaceous glands and epidermal keratinization, and that these actions are independent of any possible influence on the incidence of mitoses in these tissues.

As studied in samples of dorsal skin taken at biopsy and measured by sebaceous cell counts, the sebaceous alveoli of immature female rats increased in size for 2 days after the implantation of 1 mg. of oestradiol benzoate, and decreased progressively on days 3, 5 and 9 to a level much below normal on day 20. This was accompanied by an increase in size of the sebaceous cells which was evident by the first day after implantation. There was no subsequent decrease in size below normal. Changes in alveolar number may also have taken place.Wounding appeared to increase the size of the sebaceous glands for a distance of at least 2–8 mm. from the edge of the wound, and this effect was apparent even 1 day after wounding.

Treatment with thyrotrophic hormone (TSH) significantly enhanced the action of testosterone in increasing sebum secretion in both castrated and hypophysectomized—castrated male rats. The dose of TSH, equivalent to about 0·1 i.u./24 h for 24 days, was insufficient to increase thyroid weight, even though this was only half of normal in the hypophysectomized—castrated rats.Treatment with thyroxine (T4) significantly added to the action of testosterone in increasing sebum production in castrated rats, but the effect was accompanied by a decreased incidence of mitoses in the sebaceous glands.Treatment with propylthiouracil did not by itself affect sebaceous activity in castrated rats, nor did it inhibit the action of testosterone. Sebum secretion in castrated animals treated with propylthiouracil and testosterone was significantly higher than in those treated with testosterone alone.In view of the evidence that TSH and T4, although similar in their effects on sebum secretion, appeared to act in opposite ways on the incidence of sebaceous mitoses, and that the response of the sebaceous glands to testosterone was increased rather than inhibited by treatment of the rats with propylthiouracil, it is concluded that the action of TSH in enhancing the sebaceous response is more likely to be direct than indirect by stimulation of the thyroid gland.

Castrated rats were implanted with testosterone and in addition treated with either cyproterone acetate or oestradiol or both. Testosterone by itself very significantly increased both sebum production and the incidence of sebaceous mitoses. Each of the other compounds significantly reduced sebum production in rats treated with testosterone. Cyproterone acetate reduced the incidence of sebaceous mitoses and the weight of the preputial glands, whereas oestradiol had neither of these effects. When both compounds were given simultaneously, their combined effect in reducing sebaceous secretion was equal to the product of their individual effects. The results reinforce the view that oestrogenic and anti-oestrogenic steroids have different points of action in the sebaceous glands, and suggest that the most effective way of reducing sebaceous activity might be to use both types of compound in combination.

Progesterone, given as an implant releasing 0·1–0·2 mg./day for 24 days, failed to increase sebum production or preputial gland weight in castrated or hypophysectomized-castrated male rats. A dose of 10 mg./day in arachis oil also failed to increase sebum production or mitoses in the sebaceous glands, though it increased by 70% preputial gland weight in the presence of the pituitary.Hypophysectomy greatly reduced preputial gland wt, and the response of hypophysectomized rats to 10mg. progesterone/day was much less than when the pituitary was present. A porcine growth hormone preparation, known to facilitate the response of the sebaceous gland to testosterone in the hypophysectomized rat, failed to facilitate the response of the preputial gland to progesterone.It is concluded that 'sebum-permissive' activity (the facilitation of the response of the sebaceous gland to testosterone) may be distinct from ' sebotropic' activity (facilitation of the response of the preputial gland to progesterone), and it is argued that each of these activities may prove to be separable from somatotrophic activity.

Hypophysectomy of, or administration of thyroxine to, male or female rats advances the activity of hair follicles in the ensuing wave of growth; administration of propylthiouracil retards it. The effects seem to be more marked in the dorsal and head regions than in the flank or belly. Propylthiouracil does not prevent the activation of the follicle induced by plucking of the club hair. It is suggested that the hormonal effects may be produced indirectly through the dermis. Hypophysectomy increased definitive hair length in females but not in males; thyroxine also produced a small increase and propylthiouracil a decrease which proved to be significant in females, but not in males.

Hair growth is intermittent; periods of activity when the follicle is producing the hair alternating with periods of rest when the dead hair is retained. In the rat, hair growth occurs in a series of waves which start ventrally and pass over the flanks to the back (Dry, 1926; Butcher, 1934; Johnson, 1958).

Hair growth in the rat occurs in a series of waves, which start ventrally and pass over the flanks to the back (Dry, 1926; Butcher, 1934; Johnson, 1958a). The activity of the hair follicle is cyclic; when the hair has been fully formed there is a period of quiescence during which the dead hair is retained as a ‘club’. The duration of the complete cycle varies with site and age, ranging from 24 to about 100 days (Ebling & Johnson, 1964).

5α-Dihydrotestosterone and androstenedione (0·2 mg/24 h for 24 days), but not testosterone, significantly increased sebum production in hypophysectomized—castrated rats. Dehydroepiandrosterone and androsterone, even in doses ten times greater, could not be shown to do so, though all the steroids increased the incidence of mitoses in the sebaceous glands. In rats with intact pituitaries, however, the greatest effect on sebaceous secretion was produced by testosterone. A significant increase was also produced by 5α-dihydrotestosterone; androstenedione was only effective at ten times the dose, and androsterone was without significant effect. Dehydroepiandrosterone was not tested.A possible interpretation of the results is that within the sebaceous glands, either the release of testosterone from its conjugates or its conversion to an active metabolite is under pituitary control. The results also support the view that there are at least two distinct points of action of steroids on the sebaceous glands, namely mitosis and intracellular synthesis of sebum.

1. Castration of male albino rats, aged 30 weeks at death, caused reduction in volume of the sebaceous glands by diminishing the size of the cells and their rate of proliferation. Cell life or 'turnover time' appeared to be increased.2. Implantation of testosterone in castrated rats increased the volume of the glands by increasing the size of the cells and their rate of proliferation; at the same time cell life was reduced.3. Testosterone had no effect on the size of the sebaceous glands in hypophysectomized castrated rats.4. Nevertheless, in hypophysectomized castrated animals treated with testosterone there appeared to be larger sebaceous cells than in similar untreated animals, and a higher rate of cell proliferation in the sebaceous glands than in untreated castrated rats. The explanation of this anomaly may be that in all hypophysectomized castrated animals, and particularly in those treated with testosterone, cell life was very short. These results suggest that the pituitary does not exert a clear-cut, 'all or none' effect but rather facilitates the full action of testosterone on the sebaceous gland.5. Testosterone increased the rate of cell proliferation in the epidermis of castrated rats, but this did not affect the thickness of the Malpighian layer.6. Hypophysectomy of castrated rats significantly increased the thickness of the Malpighian layer, and this appeared to be due to an increased rate of cell proliferation over that of castrated rats rather than to an increase in the length of cell life. Testosterone did not reduce epidermal thickness in these animals.

Administration of 1 i.u./24h of adrenocorticotrophic hormone (Cortrophin ZN, ACTH) to hypophysectomized—castrated rats significantly increased sebum production to the level of that in castrated rats with intact pituitaries. The incidence of mitoses in the sebaceous glands was also significantly increased. Neither the preputial glands nor the seminal vesicles showed any response.No significant increase in sebum production in hypophysectomized—castrated rats could be detected 24 days after giving implants releasing 0·2 or 0·6 mg testosterone/24 h, although sebaceous mitoses were significantly increased in both instances. Concomitant administration of both ACTH and testosterone raised sebum production to the same extent as ACTH alone, and raised the incidence of sebaceous mitoses to a level equal to that produced by ACTH plus testosterone.It is concluded that the sebaceous glands respond—either directly or indirectly as the result of stimulation of the adrenal cortex—to ACTH and that this response is less dependent on the presence of the pituitary than is the action of testosterone. ACTH does not itself facilitate the response of the sebaceous glands to testosterone.

An anti-androgenic steroid, 17α-methyl-B-nortestosterone was shown to reduce sebum production in spayed female rats treated simultaneously with testosterone. The sebum production was assessed by measuring the increase in the amount of ether-extractable hair fat over a period of 8 days immediately after washing the rats. Testosterone increased the secretion of sebum mainly by stimulating mitosis in the sebaceous glands and it was shown that the anti-androgenic steroid acted at this site, i.e. by suppressing mitosis. These effects were in contrast to the action of oestradiol which also depressed sebaceous activity, but appeared to do so by interfering with synthesis in the sebaceous cells.