Showing papers in "Journal of Endocrinology in 1981"

Rise in plasma concentration of aldosterone during long-term angiotensin II suppression.

Abstract: The plasma concentration of aldosterone was followed in seven hypertensive patients before and during long-term angiotensin II suppression with the orally active angiotensin-I-converting-enzyme inhibitor, captopril. The plasma concentration of aldosterone decreased initially from 74 to 21 pg/ml (P less than 0.05) after 1 month of administration of captopril. Thereafter the plasma concentration of aldosterone began to rise and after 1 year reached a level of 165 pg/ml. During long-term captopril therapy the plasma renin activity remained increased and the plasma angiotensin II concentration suppressed. The mechanism responsible for the late rise of the plasma concentration of aldosterone during long-term angiotensin II suppression with captopril remains to be elucidated. A sizeable and lasting hypotensive effect was observed in all patients.

Age and mental health-related circadian rhythms of plasma levels of melatonin, prolactin, luteinizing hormone and follicle-stimulating hormone in man

Abstract: Circadian changes in plasma levels of melatonin, prolactin, LH and FSH were studied in four groups: seven healthy young men, six elderly men, six elderly women and six elderly demented patients (two men and four women). The daily activities of the subjects were synchronous and blood samples were taken every 4 h. The 24-h mean concentrations of prolactin in plasma were the same in all groups, whereas those of LH and FSh were twice as high in the elderly as in the young men and eight and 23 times higher respectively in the elderly women. The 24-h mean plasma levels of melatonin in the elderly were half those in the young, but were not influenced by the sex or mental condition of the subjects. A statistically significant circadian rhythm for melatonin was defined in the four groups, for prolactin in all groups except the elderly men and for LH only in the demented patients and in the young men. No circadian rhythm could be detected for FSH in any of the four groups. The acrophases of melatonin and prolactin ranged between 02.30 and 04.00 h, those of LH (when a rhythm was validated) clustered around 01.00 h. The circadian rhythms of plasma levels of melatonin, prolactin and LH are not modified in old age nor in dementia. A positive correlation has been demonstrated in young men between melatonin and LH and between melatonin and prolactin, but no such correlation could be found in the elderly.

The possible role of prolactin in the regulation of nesting behaviour and the secretion of luteinizing hormone in broody bantams

Abstract: The time spent each day on the nest and the rate of formation of the brood patch before the onset of incubation were measured in bantams (Gallus domesticus) and related to changes in the concentrations of plasma LH and prolactin. The hens spent progressively more time on the nest in the 5 days before the onset of incubation so that by the first day of incubation they were spending more than 90% of their time in this way. The concentration of plasma prolactin increased while that of LH fell on successive days before the onset of incubation: the increase in plasma prolactin preceded the fall in plasma LH by 2 days. The formation of the brood patch closely followed the increase in the concentration of plasma prolactin. In four out of five bantams the increase in nesting behavior was preceded by an increase in the secretion of prolactin. An injection of chicken prolactin antiserum into bantams incubating eggs resulted in a significant (P less than 0.05) increase in the plasma concentration of LH. The observations suggest that, in the bantam, the onset of incubation is initiated by an increase in the secretion of prolactin which also suppresses the secretion of LH.

Effect of injected human chorionic gonadotrophin on capillary permeability, extracellular fluid volume and the flow of lymph and blood in the testes of rats

Abstract: The subcutaneous injection of human chorionic gonadotrophin (HCG) into adult male rats caused appreciable rises in capillary permeability and lymph flow in the testis, accompanied by smaller rises in the volume of extratubular, extracellular fluid. Most of these changes were already apparent 8 h after injection, but became progressively greater during the next 12 h. Testicular blood flow was unchanged at 12 h but increased slightly between 12 and 6 h after injection. The primary effect is probably the increase in capillary permeability. The timing of these changes suggests that HCG does not affect the capillaries directly, but it would seem that the changes are due to some substances secreted by the testis in response to the HCG. It is clear that these changes will have important influences both on the access to the testicular cells of peptide hormones in the blood and also on the passage into the venous blood of hormones secreted by the testis.

Importance of variations in behavioural and feedback actions of oestradiol to the control of seasonal breeding in the ewe.

Abstract: Seasonal variations in the behavioural and feedback actions of oestradiol in the ewe were examined by determining the ability of various physiological oestradiol concentrations to elicit oestrous behaviour, induce an LH surge, and suppress tonic LH secretion at four times of the year. These tests were performed in acutely ovariectomized animals pretreated with oestradiol and progesterone to minimize seasonal differences in their endocrine status. Although smaller amplitude LH surges were observed in anoestrus, the dose-response curves for the induction of LH surges were virtually identical at all times of the year. Oestradiol was slightly less effective in eliciting oestrous behaviour in anoestrus and during the transition to the breeding season than at other times. This seasonal variation was, however, observed only with relatively low oestradiol concentrations; serum oestradiol levels of 3 pg/ml or greater induced oestrus in almost all ewes regardless of season. In contrast, there was a marked seasonal change in the negative feedback action of oestradiol. In anoestrus, basal oestradiol levels of 1-3 pg/ml suppressed LH to low levels (0.3 ng/ml), whereas in the breeding season, even peak oestradiol concentrations of 10 pg/ml were not able to produce this degree of inhibition. These results thus support the hypothesis that the annual breeding cycle of the ewe is governed primarily by shifts in the extent to which oestradiol can suppress tonic LH secretion.

Evidence that changes in luteinizing hormone secretion regulate the growth of the preovulatory follicle in the ewe.

Abstract: The aim of the present study was to gain evidence that the level of LH secretion preceding the preovulatory LH surge is an important determinant of follicular maturation and corpus luteum function in the ewe. In addition it was hoped to establish whether the pattern of LH delivery to the ovary (pulsatile v. constant) is a critical factor in the maturation of a preovulatory follicle. To accomplish this, progesterone-primed anoestrous ewes were repeatedly injected i.v. with LH or luteinizing hormone-releasing hormone (LH-RH), or given an i.v. infusion of LH, over a 72 h period. These animals, together with the appropriate controls, were exposed to a sexually active ram so that oestrous activity could be recorded. All ewes were subjected to intensive blood sampling regimes so that the plasma levels of LH and progesterone could be determined and compared to those which occurred in the same breed of sheep during the oestrous cycle. Collectively the data suggest that the plasma levels of LH preceding the preovulatory LH surge are an important determinant of follicular maturation as judged by subsequent corpus luteum function. Moreover, they show that follicular maturation can be achieved with widely differing patterns of LH delivery to the ovary during the preovulatory period and that a strict pulsatile delivery of LH may not be an absolute requirement.

Concentrations of prolactin and luteinizing hormone in plasma of doves in relation to incubation and development of the crop gland.

Abstract: The concentrations of prolactin and LH were measured in the plasma of male and female ring doves (Streptopelia risoria) during the breeding cycle. Prolactin concentrations were low during courtship and early incubation but increased markedly (P less than 0.01 in both sexes) between days 7 and 15 of incubation, during the period of rapid growth of the crop sac. Levels remained raised for 4 days after the young had hatched but then declined as the crop sacs gradually regressed. These observations showed that concentrations of prolactin were high at the time when the crop sacs were proliferating and producing 'milk' for feeding the young, but that there was no increase in prolactin secretion at the onset of incubation as occurs in ducks, hens and other birds. In samples taken from doves at various times of the day and night there was no increase in plasma prolactin during the first few days of incubation. Concentrations of LH in plasma were generally higher in male doves than in females, but in both sexes were significantly higher during courtship than during incubation and brooding the young. Concentrations increased again when the young were independent and the parents began a second round of courtship.

Changes in the plasma concentrations of luteinizing hormone, progesterone, oestradiol and testosterone and in the binding of follicle-stimulating hormone to the theca of follicles during the ovulation cycle of the hen (Gallus domesticus).

Abstract: The changes in the binding of FSH during follicular maturation were examined in the hen using 125I-labelled bovine FSH (bFSH) and unlabelled bFSH. The binding of 125I-labelled bFSH was not inhibited by bovine LH or chicken LH but was inhibited by extracts of chicken pituitary glands. The ovarian stroma, which contained both interstitial tissue and small follicles, bound the greatest amount of FSH. As the follicles progressed through the yolk-filled hierarchy of maturation, they bound decreasing amounts of FSH. In the two largest follicles of the hierarchy, there was a significant increase in the binding of FSH 12-16h before ovulation. There were two peaks in the concentrations of LH; a preovulatory peak occurred 4-6h before ovulation and a second peak occurred 14-16h before ovulation. Plasma concentrations of testosterone, oestradiol and progesterone began to rise 9, 8 and 6h, respectively, before ovulation. These data are consistent with the hypothesis that changes in the gonadotrophin concentration and binding regulate the order of the follicular hierarchy and the onset of preovulatory steroidogenesis in the hen.

Increase in the level of retinal melatonin and persistence of its diurnal rhythm in rats after pinealectomy.

Abstract: To study the short- and long-term effects of pinealectomy on the level of retinal melatonin, male rats adapted to a photoperiod of 12 h light: 12 h darkness (with lights on at 06.00 h) were pinealectomy. In the short-term experiment, the rats were decapitated 1 week after pinealectomized. In the long-term experiment, 1 month was allowed for recovery. Melatonin was extracted from retinae and quantified by radioimmunoassay. A diurnal rhythm of retinal melatonin was found to persist after pinealectomy in both experiments. An increase in retinal melatonin was demonstrated 1 month after pinealectomy, indicating a compensatory effect on melatonin in the retinae of pinealectomized rats. Thus, biosynthesis of melatonin in the retina may be modulated through a negative feedback system.

Variations in plasma concentrations of vasopressin during the menstrual cycle.

Abstract: Plasma vasopressin concentrations, determined by radioimmunoassay, were followed throughout the menstrual cycle in eight healthy women. The concentrations were found to depend on the day of the menstrual cycle. The mean concentration on day 1 was 0.5 +/- 0.08 (S.E.M.) microunits/ml, while that on days 16-18 was 1.1 +/- 0.16 microunits/ml. These values were significantly (P less than 0.02) different. Vasopressin release in women may thus depend on the hormonal changes during the menstrual cycle.

Effects of epidermal growth factor on hair growth in the mouse.

Abstract: The growth of the first hair coat in male mice was studied during administration of epidermal growth factor (EGF). Injections of 1 or 4 micrograms EGF/g body weight for 14 consecutive days from birth resulted in the development of curved overhairs (monotrichs), caused a retardation in rate of growth in length of hair and a reduction in hair diameter and length of follicle bulb. Growth rate partially recovered after cessation of EGF treatment. However, some of the effects produced by injections of EGF during the formation of the first coat were detected in the second and third generations of hair. Since EGF also retarded rate of body growth, we compared the effect of EGF on hair growth with that of restricting food intake in neonatal mice during the development of the first coat. Hair growth was slowed in underfed animals but the effects were less marked than those found in EGF-treated mice of similar body weights.

Electrophysiological recordings from oxytocinergic neurones during suckling in the unanaesthetized lactating rat.

Abstract: A method is described for making extracellular recordings of the spontaneous activity of single hypothalamic neurones in unanaesthetized, freely moving, lactating rats using chronically implanted micro-wire electrodes. Extracellular recordings taken from individual neurones were maintained for periods of between 1 and 12 days. These records were not affected by any normal movement of the animal. As several micro-wires were implanted into each animal it was possible to make simultaneous recordings from several different hypothalamic sites in the same animal. Some recordings were identified as those from magnocellular neurones in the paraventricular nucleus on the basis of antidromic invasion after electrical stimulation of the neurohypophysis. Milk ejection in response to the prolonged sucking of ten or more pups was intermittent, and individual milk ejections recurred at intervals of 2-10 min throughout each period of nursing. The rise in intramammary pressure at milk ejection was associated with a vigorous extensor response from the pups. This was monitored by radar to provide an index of milk ejection in the unanaesthetized rat. Eleven antidromically identified neurones were recorded through 321 milk ejections. Eight of these neurones displayed a transient (2-6s) and very substantial acceleration in discharge at the time predicted for oxytocin release, i.e. 10-12s before milk ejection. The background discharge of these cells was 0.1-2.6 action potentials/s; this increased to 16-50 action potentials/s during the brief period of accelerated activity. Twenty-five neurones were studied during 365 milk ejections in rats which did not have a stimulating electrode implanted in the neurohypophysis. Thirteen of these neurones displayed a burst of high frequency discharge before each milk ejection, similar to that described for the antidromically identified neurones. Two of the non-responsive cells displayed a phasic pattern of discharge, characteristic of vasopressinergic neurone discharge recorded in anaesthetized rats. These observations of putative oxytocinergic neurones in unanaesthetized, freely moving rats are identical with those previously made on anaesthetized rats, and establish that the high frequency burst of electrical activity displayed by magnocellular neurones some 10-12s before milk ejection is responsible for oxytocin release under normal physiological circumstances.

Ontogenetic development of the inhibition of growth hormone release by somatostatin in the rat: in-vivo and in-vitro (perifusion) study.

Abstract: An in-vitro study of GH secretion by rat fetal and neonatal pituitary glands was conducted using a perifusion system. After a 2 h period the GH content of the effluent was constant. Theophylline, thyrotrophin releasing hormone (TRH) and rat stalk median emience extract (SME) were effective stimuli of GH release from the pituitary glands of the 19.5-day-old fetuses. Somatostatin, added to the medium (10 microgram/ml), had no inhibitory effect on GH release (basal or stimulated by either theophylline or SME) before day 4 after birth. After postnatal day 5, somatostatin always inhibited GH secretion. These findings were consistent with the results of experiments in vivo. In rats tested within 4 days of birth, sodium pentobarbitone-stimulated plasma GH levels were not reduced by somatostatin; on day 4 and thereafter somatostatin depressed the response to pentobarbitone injection. These results indicate a postnatal maturation of the regulation of GH release by the hypothalamo-hypophysial system in the rat.

Effects of hypothyroidism on the brown adipose tissue of adult rats: comparison with the effects of adaptation to cold.

Abstract: Hypothyroidism was induced in adult rats by oral absorption of methimazole and its effects on brown adipose tissue (BAT) were studied. Hypothyroidism partially mimicked the effects of chronic exposure to cold: BAT weight and its DNA content were increased and the mitochondrial components (proteins, phospholipids) of the tissue were greatly enhanced when expressed per unit of fresh tissue weight. Moreover, hypothyroidism had the same effects as adaptation to cold on the fatty-acid composition of both total and mitochondrial phospholipids. Basal respiratory rate and total cytochrome C oxidase activity of the tissue were also increased. However, the increase in the concentration of the '32,000 mol. wt protein', a polypeptide which regulates the dissipation of heat by BAT, was smaller and non-selective in hypothyroid rats. The amount of this protein was increased per mg tissue, but not per mg mitochondrial proteins, as in rats adapted to cold. Furthermore, in contrast with the large mobilization of the lipid stores in BAT of euthyroid animals, the BAT lipid stores of hypothyroid rats were not mobilized during the first hours of exposure to cold. It may be concluded that (a) hypothyroidism induces several alterations in BAT which are characteristic of an active thermogenic state (this may be because of the response of the organism to the deficiency of thermogenesis induced by hypothyroidism), (b) this potential increase in thermogenic capacity in the BAT of hypothyroid rats has probably a limited physiological role, since thyroid hormones are necessary for the mobilization of the tissue lipids which are the fuel for production of heat and (c) these data provide evidence for a limited role of thyroid hormones in the tropic response of BAT during adaptation to cold.

Concentrations of pituitary, gonadal and adrenal hormones in serum of laying and broody white rock hens (Gallus domesticus).

Abstract: Diurnal variations in circulating concentrations of LH, GH, prolactin, corticosterone, oestradiol, progesterone and testosterone were followed in laying and broody White Rock domestic fowl. Throughout the 24 h study prolactin concentrations in serum were consistently (two- to fourfold) higher in broody than in laying birds, in which the prolactin level varied with the light:darkness or ovulatory cycles. Concentrations of GH in serum tended to be lower in broody birds but in both groups were very variable and showed no obvious relationship with either the lighting or ovulatory cycles. Broodiness was also characterized by low LH and gonadal steroid levels and by the absence of preovulatory peaks in the serum concentrations of these hormones. A diurnal rhythm in corticosterone was observed in both the laying and broody birds, with high levels during the period of darkness. Corticosterone concentrations were markedly higher in the broody birds than in laying birds during most of the 24 h study. No diurnal rhythm in the blood haematocrit level was observed in either group, although the level was generally lower in broody birds. This difference, however, was insufficient to account for the lower LH and gonadal steroid levels in the broody birds. The results suggest that prolactin is involved in the initiation or maintenance of broodiness in the fowl and the possibility of an antigonadal role for the hormone is discussed.

Androgen and oestrogen binding in cytosols of human ovarian tumours.

Abstract: The specific retention of androgens and oestrogens by cytoplasmic components of human ovarian tumours was investigated. High-affinity, low-capacity binding of androgens was observed in 88% of tumour specimens and oestrogen binding in 32%. Retention of oestrogens did not occur in the absence of androgen binding. The androgen-binding component, of sedimentation coefficient 7.5-8.5S, showed specificity for 5 alpha-dihydrotestosterone and 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881). In some instances, competition for R1881-binding sites indicated the presence of progesterone receptor-like binding. The data presented suggest strongly the existence of androgen and oestrogen receptors in some ovarian tumours and may be relevant to histopathological classification and therapeutic rationales.

Extraglandular oestrogen formation and serum binding of oestradiol: relationship to cancer.

Abstract: Recent research has attempted to find elevated levels of estradiol(E2) or other hormones in the victims of cancer or those at high risk. This literature review argues that such a search is fruitless because the mechanism defining E2 excretion metabolic clearance rate is actually the ability of E2 to bind to sex hormone binding globulin (SHBG). Hence even persons with low levels of excreted E2 may have a deficiency in binding resulting in high levels of free serum E2 in the body and excessive exposure to the hormone. A number of conditions are known to increase production of estrone from circulating androstenedion in both men and women: these include hyperthyroidism aging hepatic disease and obesity. Of particular interest is obesity since in vitro adipose tissue seems to be a site of extraglandular E2 formation. Obesity increases estrogen availability in 3 ways: 1) increased adrenal secretory activity makes more androstenedion available for conversion to estrone in peripheral tissues; 2) the efficiency of androstenedion to estrone conversion is elevated in obese subjects; and 3) most important serum SHBG seems to be markedly depressed in virtually all subjects who weight more than 25 kg above their ideal body weight. Thus lipids may interfere with E2 binding in vivo. Therefore the possibility exists that nonsteroidal lipids may interfere with E2 binding to SHBG and that dietary fats particularly those containing polyunsaturated fatty acids may promote breast cancer. This has been seen in animal studies and human epidemiological studies of cancer and extraglandular estrogen formation with decreased SHBG binding are in order.

SERUM LEVELS OF OESTRADIOL-17β AND PROGESTERONE IN RELATION TO SEXUAL RECEPTIVITY IN INTACT AND OVARIECTOMIZED RATS

Abstract: Serum levels of oestradiol-17 beta fluctuated markedly during the oestrous cycle or rats. The onset of sexual receptivity occurred in close correlation with increasing serum levels of progesterone. The serum levels of oestradiol and progesterone in ovariectomized rats implanted with constant-release implants filled with oestradiol or progesterone were related to the amount of hormone in the implants. Constant low serum levels of oestradiol stimulated sexual behaviour in ovariectomized rats, but progesterone stimulation was required for maximum behavioural responses. Peak levels of progesterone in the serum during the oestrous cycle were much higher than those needed for induction of the behaviour in ovariectomized, oestradiol-treated rats. Progesterone, administered in physiological doses, inhibited the induction of sexual receptivity caused by oestradiol and progesterone and the inhibition depended on the strength of the stimulation with oestradiol.

Effect of bovine growth hormone and a partially pure preparation of somatomedin on various growth parameters in hypopituitary dwarf mice

Abstract: The growth-promoting effects of a partially purified preparation of somatomedin (12.7 units/mg) were compared with those of various doses of bovine GH (5, 20 and 80 micrograms/day) when injected into hypopituitary dwarf mice. Growth parameters studied were body-weight and tail-length velocities (calculated as the slope of a regression line fitted to daily measurements against time), uptake of 35SO4(2-) into costal cartilage in vivo and organ weights (heart, liver and kidney). In the first experiment somatomedin (6.4 units/day), bovine GH and 0.9% NaCl were injected once daily in a volume of 0.1 ml for 10 days. Treatment with bovine GH promoted a significant dose-dependent increase in body-weight and tail-length velocities and 35SO4(2-) uptake into costal cartilage in vivo. Somatomedin also promoted a significant increase in body-weight velocity and 35SO4(2-) uptake, both responses were between that observed with the lowest dose of bovine GH and control values. Somatomedin did not promote increase in tail-length velocity. Organ weights did not differ significantly between any of the treatment groups when expressed as mg/g body weight. In the second experiment somatomedin (a daily total of 21.6 units/day) and 0.9% NaCl were injected three times per day in a volume of 0.033 ml, bovine GH was again injected once daily in a volume of 0.1 ml, and the treatment period was 12 days. As in the first experiment all doses of bovine GH and somatomedin promoted a significant increase in body-weight velocity. These results are consistent with the somatomedin hypothesis.

Dissociation in the regulation of luteinizing hormone and follicle-stimulating hormone in a hyperprolactinaemic rat model: interrelationships between gonadotrophin and prolactin control.

Abstract: Male and female Wistar rats were made hyperprolactinaemic by grafting two pituitary glands of litter-mate donors under the kidney capsule at 30 days of age. Other animals were sham-operated at the same age to serve as controls. Plasma levels of prolactin, LH and FSH were measured by double-antibody radioimmunoassay. Basal preoperative prolactin levels of approximately 10 ng/ml increased after the transplantation in both male and female rats, reaching values of approximately 180 ng/ml. Levels of LH were significantly reduced in these hyperprolactinaemic rats, whereas an increase in FSH values were seen. After administration of LH releasing hormone (LH-RH) a reduced LH response was seen but there was no response of FSH to LH-RH or even a decrease in FSH values. Prolactin levels were also reduced by LH-RH injection. Although an increase in prolactin levels was observed in control animals after a challenge with oestradiol benzoate, reduced increments were seen in experimental animals. The positive feedback effect of oestradiol benzoate on LH in females was reduced in pituitary-grafted rats but a potentiation of the FSH positive feedback could be clearly detected. This study suggests a dissociation of LH and FSH regulation in hyperprolactinaemia.

Induction of sexual receptivity in ovariectomized rats by pulse administration of oestradiol-17 beta.

Abstract: Constant-release implants filled with oestradiol-17 beta induced sexual receptivity in ovariectomized rats in response to progesterone treatment if they were implanted 32 h before behavioural testing. A 20 h period of exposure to oestradiol, by implantation 32 h before testing and removal of the implants 20 h later, was sufficient for induction of the behaviour. The exposure time necessary for behavioural responses could be further reduced to two 4 h periods, between 32 and 28 h and between 16 and 12 h, before testing. Serum levels of oestradiol were raised within 1 h of oestradiol implantation and declined rapidly after implant removal. A single injection of oestradiol benzoate was much more potent than a single injection of oestradiol in inducing sexual receptivity in ovariectomized rats, but this difference in potency was reversed if two appropriately timed injections were given. Oestrone- or oestriol-filled implants were relatively ineffective in inducing sexual receptivity. It is suggested that oestradiol has to be present at crucial time points to prepare an ovariectomized rat to respond behaviourally to progesterone treatment and that oestradiol is the principal oestrogen in the stimulation of sexual behaviour in female rats.

Response of luteinizing hormone from columns of dispersed rat pituitary cells to a highly potent analogue of luteinizing hormone releasing hormone

Abstract: The response of LH from a perfused column of dispersed rat anterior pituitary cells to LH releasing hormone (LH-RH) and the analogue, D-Ser(But)6-desGly10-Proethylamide9-LH-RH (Hoe 766), was investigated. Dose-response curves showed non-parallelism between LH-RH and the analogue. but it was evident that the analogue was considerably more potent. After a single pulse of LH-RH, LH output returned to basal values in 8 min; this was prolonged to 20 min in the case of the analogue. During this 20 min the cells were refractory to pulses of LH-RH but pulses of the analogue maintained output of LH. During constant-dose perfusion with either synthetic LH-RH or the analogue, output of LH rapidly reached a peak and then gradually fell over several hours to approach baseline values. However, a pulse of 50 mmol potassium chloride/l was still able to release LH at this time. The data are consistent with the view that this analogue of LH-RH is highly potent and is strongly bound by the LH-RH receptor. Furthermore, since it desensitizes the LH-RH receptor, it appears that continued turnover of either LH-RH or the analogue at the receptor is necessary for output of LH to be maintained.

Effect of bromocriptine on DNA synthesis, growth and hormone secretion of spontaneous pituitary tumours in the rat.

Abstract: The 'spontaneous' development of pituitary tumours has been studied in the Wistar-Furth strain of rat. In females aged 64--135 weeks the incidence was as high as 69% whereas in males aged 72--116 weeks only 6% developed tumours. Hyperprolactinaemia was invariably associated with these spontaneous pituitary tumours but excessive secretion of growth hormone (GH) was found in one animal only. Bromocriptine inhibited secretion of prolactin and DNA synthesis of the tumours. In a mixed GH- and prolactin-secreting tumour transplanted to a peripheral site, bromocriptine reduced the size of the tumour as well as the secretion of both hormones. Oestradiol reversed the inhibitory action of bromocriptine on prolactin secretion and tumour growth but failed to influence the reduction in GH secretion caused by the drug.

Interaction of alpha-melanocyte-stimulating hormone, melatonin, cyclic AMP and cyclic GMP in the control of melanogenesis in hair follicle melanocytes in vitro.

Abstract: In short-term (48 h) cultures of hair follicles alpha-melanocyte-stimulating hormone (alpha-MSH) and cyclic AMP stimulated melanogenesis through an increase in tyrosinase activity. In contrast cyclic GMP mimicked the effects of melatonin by inhibiting melanin production without causing a concomitant decrease in tyrosinase activity. Both cyclic GMP and melatonin blocked the stimulatory effects of cyclic AMP and alpha-MSH on melanin production but they left the increased levels of tyrosinase activity unaffected. Phosphodiesterase inhibitors (3-isobutyl-1--methylxanthine and papaverine) simultaneously stimulated tyrosinase activity and inhibited melanin production, presumably by allowing endogenous cyclic AMP and cyclic GMP to accumulate intracellularly. It is suggested that whereas MSH stimulates melanogenesis through a cyclic AMP-dependent mechanism there must also be an inhibitory cyclic GMP-dependent mechanism, perhaps activated by melatonin, which operates at some post-tyrosinase step in the melanin biosynthetic pathway.

Uterine oestrogen and progesterone receptors in the ovariectomized rat.

Abstract: The effect was studied of repeated injections of oestradiol-17 beta (5, 10, 25, 50 micrograms) given for various lengths of time (3, 5, 9 days) on total cell content of oestrogen receptors and cytosol progesterone receptors in the uteri of ovariectomized rats. An additional group of rats was injected daily with 50 micrograms oestradiol benzoate (OB) for 9 days in order to achieve a more sustained concentration of oestradiol in the blood. Injections were begun 24h after ovariectomy and the rats were killed 24h after the last injection. Daily administration of 5 micrograms oestradiol prevented the initial transient rise in oestrogen receptors which was observed in the uteri of untreated rats after ovariectomy. Repeated injections of 10 micrograms oestrogen produced an initial lowering in oestrogen receptors after 3 days of treatment which was followed by a prompt rise at 5 and 9 days when treatment was continued. A significant reduction in oestrogen receptors occurred at all times studied when rats were injected daily with 25 and 50 micrograms oestradiol. A more profound reduction in oestrogen receptors was observed in the group of rats treated for 9 days with 50 micrograms OB. Synthesis of progesterone receptors was stimulated by all doses of oestrogen studied. Concentrations of progesterone receptors were significantly higher after 3 and 5 days of treatment with 25 and 50 micrograms oestrogen. After 9 days of treatment, however, concentrations of progesterone receptors were virtually identical in all treated groups, including the group treated with OB. We have concluded that large doses of oestrogen significantly decrease oestrogen receptor content in the rat uterus, especially when OB is used. The degree of reduction, however, is only moderate under these experimental conditions and is insufficient to inhibit synthesis of progesterone receptors.