bluuebunny/crossref_metadata_2025 huggingface dataset:
MEASUREMENT OF THE INTEGRATED CONCENTRATION OF PROLACTIN IN NORMAL SUBJECTS AND PATIENTS WITH HYPERPROLACTINAEMIA
Authors: DAGGETT P. R. , NABARRO J. D. N.
Published: December 2008

To determine whether the fluctuations in the concentration of prolactin in plasma of man affect diagnostic procedures, the integrated concentration of prolactin has been compared with a basal concentration. A continuous sampling apparatus was used to study nine normal subjects and 12 subjects with features of the hyperprolactinaemia syndrome. Small differences were demonstrated, which were, however, neither statistically significant nor likely to influence clinical decisions. It is concluded that single estimations of the concentration of prolactin in blood, taken under resting conditions, are adequate for routine diagnostic use.
THYMUS AND THE ENDOCRINE SYSTEM: OVARIAN DYSGENESIS IN NEONATALLY THYMECTOMIZED RATS
Authors: HATTORI M. , BRANDON M. R.
Published: December 2008

By 10 days after neonatal thymectomy, the areas of lymphocytic depletion were being repopulated by plasma or reticular cells. Subsequently, ovarian dysgenesis was observed in 50-day-old thymectomized female rats as hyperplasia of ovarian interstitial cells and an enhanced degeneration of follicles. Thymectomized rats at 130 and 170 days of age showed complete ovarian dysgenesis, testicular atrophy, hypertrophy of pituitary β-cells with pronounced cytoplasmic haloes, and lymphocytic infiltration in the pituitary, thyroid and prostate glands. These results suggest that neonatal thymectomy may initially influence the lymphoid organs (i.e. the immune system) and that changes in the immune system may result in the autoimmune-like damage in the endocrine organs and the prostate gland.

Associated with these changes, the concentrations of plasma progesterone and 17α-hydroxyprogesterone were significantly reduced in 130-day-old thymectomized female rats with respect to the sham-thymectomized controls. The concentration of plasma oestradiol-17β in thymectomized female rats was the same as in sham-thymectomized female rats. These results suggest that gestagens may normally suppress immune responses but that, in the case of thymectomized female rats, the reduced levels of gestagens may lead to enhanced immune responses.
SERUM LEVELS OF GONADOTROPHINS IN HAMSTERS EXPOSED TO SHORT PHOTOPERIODS: EFFECTS OF ADRENALECTOMY AND OVARIECTOMY
Authors: BITTMAN E. L. , GOLDMAN B. D.
Published: December 2008

Female hamsters rendered acyclic by exposure to short photoperiods (10 h light: 14 h darkness) showed diurnal surges of both LH and FSH which persisted after removal of the ovaries and adrenal glands. The reduced increase in gonadotrophin secretion after ovariectomy, typical of hamsters exposed to short days, was also not contingent upon the presence of the adrenal glands. The results demonstrate that 'supersensitivity' of the neuroendocrine axis to feedback of ovarian or adrenal steroids cannot fully account for either the daily surges of gonadotrophins or the diminished response of LH and FSH to ovariectomy in hamsters maintained on short days. It is suggested that these changes result instead from other pineal-mediated actions of short photoperiods upon the brain.
SOMATOMEDIN-LIKE ACTIVITY IN PLASMA AFTER FOETAL HYPOPHYSECTOMY OR NEPHRECTOMY AND IN EXPERIMENTAL INTRA-UTERINE GROWTH RETARDATION IN SHEEP
Authors: FALCONER J. , FORBES J. M. , HART I. C. , ROBINSON J. S. , THORBURN G. D.
Published: December 2008

Plasma samples from pregnant ewes and their foetuses during the last quarter of gestation were assayed for somatomedin-like activity (SLA) using the porcine costal cartilage assay. In maternal plasma, the mean potency (compared with pooled serum from six sheep) was 0·84 ± 0·05 (s.e.m.) units/ml (n = 15). Somatomedin-like activity in the plasma of five control foetuses (0·91 ± 0·1 units/ml) was similar to the maternal levels and did not change with gestational age. After foetal hypophysectomy the SLA in foetal plasma (0·37 ± 0·05 units/ ml, n = 4) was significantly less than in control animals. In two nephrectomized foetuses, the mean SLA in plasma (0·08 and 0·51 units/ml respectively) was less than in control animals. Retardation of intra-uterine foetal growth was induced by removal of endometrial caruncles before pregnancy in four sheep. The SLA in plasma from these foetuses was 0·38 ± 0·05 units/ml (P< 0·01 v. control animals). The results suggest that SLA in the foetus may be important in the regulation of foetal growth, but they also indicate that factors other than growth hormone may be important in the control of SLA in foetal plasma.
IMMEDIATE RESPONSE OF 5-METHOXYTRYPTOPHOL IN THE CIRCULATION TO HYPOGLYCAEMIC STRESS INDUCED BY INSULIN
Authors: HOOPER R. J. L. , SILMAN R. E. , LEONE R. M. , FINNIE M. D. A. , CARTER S. J. , SAVAGE M. , PREECE M. , SMITH I. , MULLEN P. E.
Published: December 2008

Pineal indoles have been shown to affect the release of anterior pituitary hormones but details of the interrelationships are lacking. Using a new gas chromatography–mass spectrometry (g.c.–m.s.) assay the concentration of 5-methoxytryptophol (ML) was measured in plasma samples obtained from 16 children undergoing investigation of pituitary function for delayed growth. All the children received an insulin tolerance test (ITT) to study their endocrine response to stress. Some children received luteinizing hormone releasing hormone (LH-RH) and/or thyrotrophin releasing hormone (TRH). The change in concentration of ML during an ITT was similar to the change in concentration of blood sugar; a drop at 20 min followed by a rise at 30 min. This was not significantly altered by the administration of LH-RH or TRH, nor was there a different pattern of response in children who were deficient in growth hormone as opposed to those with idiopathic delayed growth. The fall in concentration of ML with stress may mediate the increased secretion of pituitary hormones. Alternatively, the pineal gland may respond directly to insulin.
OESTROGEN CONTENT OF THE UTERINE TISSUES OF MICE AND THEIR RELATIONSHIP TO EPITHELIAL CELL PROLIFERATION AFTER SUBCUTANEOUS AND INTRALUMINAL ADMINISTRATION OF HORMONES
Authors: FAGG BARBARA , MARTIN L.
Published: December 2008

The oestrogen content of the separated uterine tissues (epithelium, stroma and myometrium) of mice was determined at various times between 1 and 24 h after administration of [3H]oestradiol or [3H]oestriol either subcutaneously or directly into the uterine lumen. After subcutaneous injections, the oestrogen levels of both the stroma and myometrium declined steadily from a maximum at 2–4 h after injection and more oestradiol than oestriol was always present. In contrast, the epithelium contained more oestriol than oestradiol and the levels of both hormones remained fairly constant over the period studied. However, a smaller percentage of the epithelial oestriol than of oestradiol was associated with the nuclear fraction. On the contrary, after intraluminal injections, the oestrogen content of all the separated tissues decreased from a maximum at 1–2 h and more oestradiol than oestriol was retained in all cases. A high proportion of the total epithelial content of both oestrogens was recovered in the nuclear fraction.

The uterine proliferative response after intraluminal injection of oestradiol or oestriol was qualitatively and quantitatively similar to that observed after subcutaneous injection of hormone, indicating that the efficacy of the oestrogens is not markedly dependent on the route of administration. These data support current concepts of oestrogen action in the uterus but indicate that studies of the whole organ may not, in all respects, be extrapolated to the individual target tissue. The importance of nuclear hormone levels as the determinant of the oestrogenic response is also emphasized.
SUPPRESSION OF PITUITARY SECRETION OF FOLLICLE-STIMULATING HORMONE BY PORCINE FOLLICULAR FLUID DURING PRO-OESTRUS AND OESTRUS IN THE RAT: EFFECTS ON GONADOTROPHIN AND STEROID SECRETION, FOLLICULAR DEVELOPMENT AND OVULATION DURING THE FOLLOWING CYCLE
Authors: DEPAOLO L. V. , HIRSHFIELD ANNE N. , ANDERSON L. D. , BARRACLOUGH C. A. , CHANNING CORNELIA P.
Published: December 2008

In this study, we have examined whether the suppression of raised plasma FSH concentrations at pro-oestrus and/or oestrus by porcine follicular fluid (PFF) affected the development of follicles for ovulation in the next cycle. Adult, 4-day-cyclic rats were injected with PFF or pig serum at various hours of pro-oestrus and oestrus. Plasma FSH levels were suppressed following PFF treatment at any time of pro-oestrus and oestrus. Furthermore, this suppression was always followed by a 'rebound' increase in plasma FSH. In contrast, plasma LH concentrations were unaffected by PFF treatment and neither gonadotrophin was altered by treatment with pig serum.

When rats treated with PFF or pig serum were allowed to complete one additional cycle, plasma LH and FSH concentrations at the pro-oestrus and oestrus after treatment were not significantly different among groups regardless of treatment or time of treatment. All ovaries of rats treated with PFF or pig serum on the next pro-oestrus morning before ovulation were histologically similar. Furthermore, all animals ovulated a normal complement of ova at the next oestrus regardless of whether preovulatory, secondary or both increases of plasma FSH had been blocked by PFF treatment during the previous cycle. However, in animals given PFF during the preceding cycle, plasma oestradiol and progesterone concentrations were significantly altered on the morning and afternoon of pro-oestrus respectively.

These results suggest that increased plasma FSH concentrations at pro-oestrus and oestrus may not be essential for folliculogenesis and ovulation in the subsequent cycle. Alternatively, the 'rebound' of FSH on day 1 of dioestrus after the suppression of both phases of FSH secretion at pro-oestrus and oestrus may be sufficient to provide ovulatory follicles for the next pro-oestrous day.
INDUCTION OF ANDROGEN-DEPENDENT PROTEASE AND SEROUS-LIKE GRANULES BY TRI-IODOTHYRONINE IN THE SUBMANDIBULAR GLAND OF MICE WITH TESTICULAR FEMINIZATION
Authors: HOSOI KAZUO , KOBAYASHI SHIZUKO , UEHA TAKAO , MARUYAMA SHICHIRO , SATO SEIICHI , TAKUMA TAISHIN , KUMEGAWA MASAYOSHI
Published: December 2008

Esteroprotease, an androgen-dependent enzyme of the mouse submandibular gland, was increased by injection of tri-iodothyronine (T3) in mice with testicular feminization (Tfm) which are genetically deficient in androgen receptors. Histochemical and electron microscopic studies also demonstrated increases of RNA and serous-like granules in cells of the convoluted tubules of the gland. These findings suggest that the esteroprotease gene in Tfm mice is normal and that T3 can induce both esteroprotease and serous-like granules independently of androgen.
AUTORADIOGRAPHIC STUDY OF LYSINE AND ARGININE INCORPORATION STIMULATED BY FOLLICLE-STIMULATING HORMONE IN THE MOUSE TESTIS IN VIVO
Authors: DAVIES A. G. , LAWRENCE N. R.
Published: December 2008

Hypophysectomized adult mice were given injections of highly purified FSH 12 h before killing, and of tritiated lysine or arginine 2 h before killing. Autoradiographs were prepared from paraffin wax sections of testes. Treatment with FSH increased the density of silver grains over the nuclei of the Sertoli cells and of all types of germinal cell except the early spermatids. The stimulatory effect of FSH on incorporation of both lysine and arginine was most marked in the nuclei of preleptotene primary spermatocytes. The ratio of arginine to lysine incorporation was greater in spermatids undergoing nuclear elongation than in other types of cell.
CIRCA-ANNUAL RHYTHMS OF PROLACTIN SECRETION IN EWES AND THE EFFECT OF PINEALECTOMY
Authors: MUNRO C. J. , McNATTY K. P. , RENSHAW L.
Published: December 2008

Changes in the plasma concentration of prolactin in intact, pinealectomized, shampinealectomized, ovariectomized and hysterectomized ewes were investigated over a period of 11 months.

The concentrations of prolactin were consistently low (<20 ng/ml) during the winter months (short photoperiod) in the intact, sham-pinealectomized, ovariectomized and hysterectomized animals. In contrast, the concentrations of prolactin were consistently raised (> 50 ng/ml) during the summer months (long photoperiod) in the same groups. During the transitional period from winter to summer the concentrations of prolactin were correlated with the reproductive status of the animals. In the pregnant animals, the prolactin concentrations increased from low values during pregnancy to high values at parturition. During lactation, the concentrations of prolactin in these animals remained high, although they were lower than those found subsequently during the summer months when the ewes were no longer lactating. In the non-pregnant ewes (i.e. the ovariectomized and hysterectomized animals), the prolactin concentrations increased more gradually during the transitional period from winter to summer than was the case in the parturient animals.

In the pinealectomized ewes, the plasma concentrations of prolactin were raised throughout the year, irrespective of whether the animals were pregnant, lactating or in anoestrus. In these animals, the only occasion when prolactin concentrations were consistently low was during the mid-winter period, although they were also low at times during the period of oestrous activity.

It was concluded that the circa-annual pattern of prolactin concentrations in ewes is primarily determined by the photoperiod, and that the pineal gland in the ewe is an important translator of the photoperiod. Parturition and suckling have important, but secondary, influences. Moreover, it was concluded that the secretions from the reproductive tract and the seasonal variations in temperature normally have little influence by themselves on the circa-annual rhythm of prolactin.
IN-VITRO STEROIDOGENESIS OF NEWLY FORMED CORPORA LUTEA AND THE NON-LUTEAL OVARY IN THE RAT, RABBIT, HAMSTER AND GUINEA-PIG
Authors: TERRANOVA P. F. , SAIDAPUR S. K. , GREENWALD G. S.
Published: December 2008

The steroidogenic abilities of the newly formed corpus luteum (8–10 h after ovulation) and the non-luteal ovary were compared in the guinea-pig, hamster, rabbit and rat using an invitro incubation technique. Histologically, newly formed rat corpora lutea (CL) were highly luteinized whereas the CL of the rabbit and guinea-pig were only partially luteinized. The CL of the hamster showed the least amount of luteinization.

Serum progesterone was highest in the rat (18 ± 3 (s.e.m.) ng/ml). In the hamster, it was about 8 ng/ml, whereas in the rabbit and guinea-pig it was about 1 ng/ml. Serum androstenedione ranged between 0·5 and 1 ng/ml. Serum testosterone was lowest in the hamster (60 pg/ml) and highest in the rabbit (470 pg/ml), whereas in the rat and guinea-pig, testosterone levels were similar (about 240 pg/ml). Serum oestrogens were at baseline levels in all species.

The CL of the rat exhibited considerably greater steroidogenic ability than the CL of the other species, producing 70 ± 6 ng progesterone/mg per h, 215 ± 14 pg androstenedione/mg per h, 49 ± 3 pg testosterone/mg per h, 3 pg oestrone/mg per h and 1 pg oestradiol/mg per h. Rabbit CL produced only progesterone (7 ± 2 ng/mg per h). Newly formed hamster CL produced none of the above steroids. In general, the ability of the CL to produce progesterone in vitro correlated with the degree of luteinization found by histological observation. Guinea-pig CL were embedded deeply in the ovary and could not be obtained without damage. Consequently, a portion of the ovary containing a corpus luteum was incubated. There was no difference in the steroid production by this portion of the ovary compared with the non-luteal ovary.

The non-luteal ovary of the rat produced the highest amount of progesterone (10 ± 2 ng/mg per h). The guinea-pig non-luteal ovary produced about 5 ± 2 ng progesterone/mg per h, whereas the non-luteal ovary of the rabbit did not produce any. On the other hand, the hamster non-luteal ovary lost progesterone. Non-luteal ovaries from all species produced androgens. The non-luteal ovary of the guinea-pig contained especially large numbers of atretic antral follicles. The guinea-pig non-luteal ovary produced extremely large amounts of androstenedione (1110 ± 210 pg/mg per h) and testosterone (606 ± 154 pg/mg per h) compared with the amounts produced by the non-luteal ovary of the rat, hamster and rabbit. In the non-luteal ovary, interstitium and atretic antral follicles are the probable source of androgens.

Oestrogen production by the non-luteal ovary was at baseline levels in the four species studied correlating with the absence of healthy antral follicles. The results indicate the extreme species differences that exist in ovarian function in the early postovulatory period.
STUDIES ON THE PRESENCE OF VASOPRESSIN, OXYTOCIN AND VASOTOCIN IN THE PINEAL GLAND, SUBCOMMISSURAL ORGAN AND FETAL PITUITARY GLAND: FAILURE TO DEMONSTRATE VASOTOCIN IN MAMMALS
Authors: DOGTEROM J. , SNIJDEWINT F. G. M. , PÉVET P. , SWAAB D. F.
Published: December 2008

The demonstration of vasotocin in the mammalian pineal gland, subcommissural organ and fetal pituitary gland by bioassay has led to hypotheses regarding the function of this hormone in various reproductive processes.

Preliminary examinations of the pineal gland and subcommissural organ with a specific radioimmunoassay failed to show vasotocin immunoreactivity. The presence of vasotocin, vasopressin and oxytocin in the pineal gland, subcommissural organ and fetal neurohypophysis was therefore investigated, using three specific radioimmunoassays. Frog and chicken pituitary glands were used to validate the vasotocin radioimmunoassay.

Direct measurements in diluted homogenates of pituitary glands from frogs, chickens, mid-term fetal sheep and near-term fetal seals revealed the presence of vasotocin only in the frog and chicken pituitary glands, while vasopressin and oxytocin were found in the two fetal pituitary homogenates.

Vasopressin and oxytocin were measured in homogenates of rat and bovine pineal glands and in preparations of the subcommissural organ of rats and rabbits after extraction with Vycor glass powder, but no specific vasotocin immunoreactivity was observed. These results indicate a discrepancy between the reported biological activity of vasotocin in the pineal gland, subcommissural organ and fetal pituitary gland and the immunoreactivity of this material, which can at present only be explained by the presence of a peptide which is structurally closely related to, but not identical with, vasotocin.
EFFECT OF ADRENOCORTICOTROPHIN ON INTRACELLULAR CHOLESTEROL TRANSPORT
Authors: NAKAMURA MASAHISA , WATANUKI MASAAKI , TILLEY B. E. , HALL P. F.
Published: December 2008

The rate of side-chain cleavage of cholesterol by mitochondria derived from mouse adrenal tumour cells was measured. Incubation of the cells in the presence of adrenocorticotrophin (ACTH) for periods of up to 1 h was without effect on the subsequent side-chain cleavage by mitochondria. However, if the cells were incubated in the presence of aminoglutethimide phosphate (0·76 mmol/l), addition of ACTH (final concentration 86 u./l) to the medium containing the cells increased the subsequent rate of side-chain cleavage by the isolated mitochondria. This response reached a maximum after incubation of cells with ACTH for 2 h and decayed when the isolated mitochondria were left at 0 °C, although a significant difference was still apparent after 120 min. Similar stimulation of mitochondrial side-chain cleavage by ACTH was observed when the reaction was inhibited by anaerobiosis instead of aminoglutethimide phosphate. Addition of dibutyryl cyclic AMP, at final concentrations greater than 10−5 mol/l, to cells during incubation with aminoglutethimide phosphate (0·76 mmol/l) also stimulated the conversion of cholesterol to pregnenolone by the mitochondria.

Provided the adrenal tumour cells were incubated with aminoglutethimide, or anaerobically, the mean cholesterol content of the inner mitochondrial membrane was significantly higher (P < 0·01) when ACTH was included in the incubation medium than when it was not.

It is concluded that ACTH increases the movement of cholesterol to the mitochondrial membrane which contains the side-chain cleavage enzyme system and that part of this cholesterol is used for the enhanced conversion of cholesterol to pregnenolone brought about by ACTH.
CLOACAL GLAND OF THE JAPANESE QUAIL: ANDROGEN DEPENDENCE AND METABOLISM OF TESTOSTERONE
Authors: MASSA R. , DAVIES D. T. , BOTTONI L.
Published: December 2008

A cloacal gland complex whose growth and development is androgen-dependent exists in the Japanese quail. In-vitro incubation studies of the cloacal gland using 4-14C-labelled testosterone as substrate allowed the positive identification of five metabolites: androstenedione, 5β-dihydrotestosterone (5β-DHT), 5β-androstane-3α,17β-diol, 5α-DHT and 5α-androstane-3α,17β-diol. More polar metabolites, not yet chemically identified, were detected in trace amounts. Androstenedione appeared to be the main testosterone metabolite in immature birds while in mature birds on long daylengths testosterone was preferentially metabolized to 5α-DHT. This change may have been in response to the higher levels of plasma steroids found in mature birds. When various testosterone metabolites, contained in silicone elastomer capsules, were implanted s.c. into castrated birds maintained on a photostimulatory light régime, 5α-DHT, 5α-androstane-3,17-dione, androstenedione and 5α-androstan-3α-ol-17-one were shown to be equipotent with testosterone in stimulating the development of the cloacal gland. 5α-Androstane-3α,17β-diol and 5α-androstan-3β-ol-17-one stimulated some growth while 5β-DHT, 5α-androstane-3β,17β-diol, 5α-androstane-3α,17β-diol, 5β-androstane-3,17-dione, androst-5-en-3β-ol-17-one and androst-5-ene-3β,17β-diol were completely ineffective.
LESIONS OF THE SUPRACHIASMATIC NUCLEI AND THE SEROTONIN-DEPENDENT PHASIC RELEASE OF LUTEINIZING HORMONE IN THE RAT: EFFECTS ON DRINKING RHYTHMICITY AND ON THE CONSEQUENCES OF PREOPTIC AREA STIMULATION
Authors: COEN C. W. , MacKINNON P. C. B.
Published: December 2008

Ovariectomized rats in which <7% of the suprachiasmatic nuclei had been spared by bilateral radiofrequency lesions were distinguishable from those with >40% of the nuclei by their consistent failure to show the oestrogen-induced daily surge of LH, either with or without pharmacological manipulations of serotonin (5-HT), and also by their loss of the normal rhythmicity of drinking. Minor damage to structures adjacent to the suprachiasmatic nuclei was similar in both groups. The identical facility with which electrical stimulation of the preoptic area induced LH release in the two groups of animals suggested that they were not characterized by different degrees of damage to the preopticotuberal pathway. These results are considered in relation to evidence indicating that the suprachiasmatic nuclei represent the densest concentration of 5-HT terminals in the forebrain and also the site of a mechanism involved in the generation of circadian rhythms.
EFFECT OF LUTEINIZING HORMONE ON PROGESTERONE SECRETION IN VITRO BY THE GRANULOSA CELLS OF THE DOMESTIC FOWL (GALLUS DOMESTICUS)
Authors: WELLS J. W. , GILBERT A. B. , CULBERT J.
Published: December 2008

During short periods of incubation (3 h) the secretion of progesterone by granulosa cells from the largest preovulatory follicle of the fowl was higher (160 pmol/μg DNA) with ovine LH in the medium than without it (60 pmol/μg DNA). Granulosa cells from follicles collected 24 and 48 h before their expected ovulation secreted progesterone at similar rates to cells from the largest follicle which was likely to ovulate within 5 h. The identity of progesterone was confirmed by physicochemical methods.

After granulosa cells had been incubated with LH in Medium 199 for 24 h, the concentration of progesterone in the medium was 1·65 μmol/l whereas oestrone and oestradiol were present at concentrations of 254 and 199 pmol/l respectively.

The results indicate that the larger yellow yolk-filled follicles of the ovarian hierarchy in the domestic fowl contribute to the preovulatory surge of progesterone which has been observed in the peripheral blood.
OESTROGEN RECEPTOR IN THE BABOON ENDOMETRIUM: CYTOSOLIC RECEPTOR, DETECTION, CHARACTERIZATION AND VARIATION OF ITS CONCENTRATION DURING THE MENSTRUAL CYCLE
Authors: MARTEL DOMINIQUE , MALET CATHERINE , OLMEDO CLAUDIO , MONIER MARIE-NOELLE , DUBOUCH PIERRE , PSYCHOYOS ALEXANDRE
Published: December 2008

A cytosolic oestrogen receptor from baboon endometria was detected and partially characterized. The apparent dissociation constant for oestradiol was 1·5 × 10−10–4 × 10−10 mol/l. Steroids that competed with the [3H]oestradiol binding to the receptor were oestradiol and ethynyloestradiol > oestriol > oestrone; progesterone, testosterone and corticosterone were not competitors. The [3H]oestradiol–receptor complexes migrated as a 3–3·5S peak during sucrose density-gradient centrifugation when endometrial samples were taken during either the proliferative or the secretory phase. A 7S peak was observed for samples taken at the period of ovulation. A [3H]oestradiol exchange technique was used to detect changes in the receptor concentration during the menstrual cycle. This concentration which was high during the early follicular phase fell sharply before the ovulatory peak of ovarian oestrogens. It remained at a base level during the early secretory phase and then rose during the last days of the cycle to the same concentration as that measured at the beginning of the cycle.
INTERACTION BETWEEN GLUCOSE AND NATURALLY OCCURRING DIABETOGENIC SUBSTANCE IN THE INDUCTION OF INSULIN RELEASE FROM ISLETS OF HYPOPHYSECTOMIZED RATS
Authors: LARSON B. A. , WILLIAMS T. L. , SHOWERS M. O. , LEWIS U. J.
Published: December 2008

Naturally occurring diabetogenic substance (NDS), isolated from clinical grade human growth hormone (hGH), induces insulin release from isolated pancreatic islets of hypo-physectomized rats in the presence of Krebs–Ringer bicarbonate solution (KRB) containing 2·8 mmol glucose/l. To determine the role of extracellular glucose in insulin release mediated by NDS, islets were perifused with glucose-free KRB containing 200 μg NDS/ml. Under these conditions NDS induced prompt insulin release (284 ± 34 (s.e.m.)% over basal insulin secretion) (P < 0·0005). Islets perifused with 16·7 mmol glucose/l before and during exposure to 200 μg NDS/ml released additional insulin with exposure to NDS (199 ± 28% over basal insulin secretion) (P< 0·0005). Purified intact hGH (200 μg/ml) did not induce insulin release in the presence of 16·7 mmol glucose/l. Mannoheptulose (5 mmol/l) did not inhibit insulin release mediated by NDS but did inhibit insulin release stimulated by 16·7 mmol glucose/l (P< 0·0005). Islets were pre-incubated for 90 min with 200 μg NDS/ml or 200 μg intact hGH/ml KRB and 2·8 mmol glucose/l to determine what effect either protein might have on subsequent glucose-stimulated (16·7 mmol/l) insulin release. Islets pre-incubated with NDS responded with no less insulin release than islets pre-incubated with intact hGH. Naturally occurring diabetogenic substance initiated insulin release in the absence of extracellular glucose, stimulated additional secretion in the presence of stimulatory glucose concentrations and did not inhibit subsequent islet response to glucose. Naturally occurring diabetogenic substance did not depend on glucose phosphorylation to initiate insulin release.
IODINATION OF THYROID-STIMULATING HORMONE FOR RECEPTOR-BINDING STUDIES WITH HUMAN THYROID MEMBRANES: EFFECTS OF SPECIFIC ACTIVITY AND METHOD OF IODINATION
Authors: KERMODE J. C. , THOMPSON B. D.
Published: December 2008

Three different methods were compared for 125I-labelling of thyroid-stimulating hormone (TSH) for use in receptor-binding studies with human thyroid membranes: these were the chloramine-T, Bolton–Hunter and lactoperoxidase methods. Chloramine-T proved to be an inferior method to the other two. Iodinations to different specific activity (0·7–9·4 Bq/pg) were also compared: too high a specific activity led to reduced binding and a dramatic shift in the pH optimum for the TSH–receptor interaction.

A specific activity of 2·5 Bq/pg should not be exceeded if binding of 125I-labelled TSH is to be representative of the binding of the natural hormone. Under these conditions, pH 7·5 was optimal for binding of TSH to its receptor. Repurification of the labelled TSH by receptor adsorption also proved to be essential.
EFFECTS OF TESTOSTERONE PROPIONATE AND CYPROTERONE ACETATE ON CARBOHYDRATE METABOLISM IN RAT MAMMARY GLANDS
Authors: DESHPANDE N. , MITCHELL IRENE
Published: December 2008

The effects of administration of testosterone propionate on the activities of seven of the enzymes of carbohydrate metabolism in normal rat mammary glands were investigated and the validity of the results was confirmed by simultaneous injection of the hormone and cyproterone acetate. The administration of the androgen increased the activities of phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and lactate dehydrogenase (LDH) in glands from both intact and from ovariectomized and adrenalectomized animals. Administration of cyproterone acetate alone resulted in a significant reduction in the activities of PFK and G6PDH and when given together with the androgen it inhibited increases in the activities of PFK, G6PDH, 6PGDH and LDH induced by testosterone. It was concluded that these results did not explain the known inhibitory effects of the androgen on normal mammary gland growth and function.
CONCENTRATIONS OF MELATONIN IN THE PLASMA OF THE RHESUS MONKEY (MACACA MULATTA)
Authors: JENKIN G. , MITCHELL M. D. , HOPKINS P. , MATTHEWS C. D. , THORBURN G. D.
Published: December 2008

A radioimmunoassay for the determination of concentrations of melatonin in the plasma of rhesus monkeys has been developed. Antiserum for the assay was raised against N-acetyl serotonin and there was a 100% cross-reaction with melatonin. Cross-reactivity with closely related indoles, precursors and metabolites was less than or equal to 1%. The lower limit of sensitivity of the assay was 4 pg/tube.

The assay has been used for the investigation of diurnal variations and cyclical changes in melatonin concentrations in peripheral plasma of the rhesus monkey. The concentrations of melatonin ranged between 26·6 and 85·3 pg/ml during sampling for 24 h.There was a distinct diurnal variation in the concentration of melatonin in plasma. The concentration during darkness (61·0 ± 7·1 (s.e.m.) pg/ml) was greater (P <0·01) than that during illumination (40·1 ± 6·1 pg/ml). There were no significant differences in the concentration of melatonin in plasma at any time during the 28 day menstrual cycle of the rhesus monkey.
FOLLICULAR DEVELOPMENT IN THE ADULT GUINEA-PIG AND RESPONSES TO HUMAN CHORIONIC GONADOTROPHIN
Authors: PEDDIE M. J.
Published: December 2008

The development of antral follicles and of atretic follicles throughout the cycle of adult guinea-pigs is a continuous process, but there are two stages when atresia is most pronounced: immediately after oestrus and in the late luteal phase. New atretic antral follicles were not found in the ovaries until around day 10 of the cycle, when an injection of HCG caused atresia of the medium-sized antral follicles within the ovary and luteinization of the largest follicles but spared the smallest antral follicles. Following the induced atresia, cycle lengths were prolonged, but the population of antral follicles could be restored to normal within 10 days of gonadotrophin treatment.

It is suggested that the growth rate of antral follicles is flexible and proceeds most rapidly at the end of the luteal phase. It is not clear whether ovarian steroids play an integral part in regulating follicular growth and atresia.
PARALLEL EFFECTS OF LIGHT SIGNALS ON THE CIRCADIAN RHYTHMS OF RUNNING ACTIVITY AND OVULATION IN RATS
Authors: SRIDARAN R. , McCORMACK C. E.
Published: December 2008

Continuous monitoring of wheel-running activity and determination of the time of ovulation in rats by serial laparotomies revealed that ovulation followed the onset of running at prooestrus by approximately 9 h (range 7–11 h). This temporal relationship held in rats in which the period of the circadian rhythm had been modified (entrained) by daily exposure to 14 h photoperiods, and in rats in dim continuous light whose rhythms were non-entrained (freerunning). Knowledge of this temporal relationship between the two rhythms made it possible to give bright light signals at known points in the circadian cycle of the rat and to observe the effects on the timing of running and ovulation in subsequent cycles. Giving daily light signals near the onset of running (i.e. at subjective dusk) delayed, whereas giving signals near the end of running (i.e. at subjective dawn) advanced, the time of running and ovulation in subsequent cycles. These results indicate that in rats exposed to the usual laboratory photoperiod the delaying effect of dusk light and the advancing effect of dawn light balance one another; thus the preovulatory surge of LH occurs at a relatively consistent time at prooestrus.
EVIDENCE FOR PREFERENTIAL STIMULATION OF GASTRIC INHIBITORY POLYPEPTIDE SECRETION IN THE RAT BY ACTIVELY TRANSPORTED CARBOHYDRATES AND THEIR ANALOGUES
Authors: SYKES S. , MORGAN L. M. , ENGLISH J. , MARKS V.
Published: December 2008

A rat intestinal perfusion technique has been used to assess the ability of a number of monosaccharides, monosaccharide analogues and disaccharides to stimulate intestinal release of immunoreactive gastric inhibitory polypeptide (GIP).

Perfusates containing glucose, sucrose, galactose, maltose, 3-O-methylglucose or α- or β-methylglucoside at concentrations of 100 mmol/l in Krebs–Ringer phosphate buffer (KRP) produced significant stimulation of GIP release compared with the control perfusions with KRP alone (P < 0·02). Mannose, 6-deoxygalactose, 2-deoxyglucose, myoinositol, fructose or lactose (100 mmol/1 of each) did not stimulate GIP release compared with controls. There was no significant difference in the ability of sucrose, maltose or β-methylglucoside (100 mmol/1 of each) to release GIP compared with 100 mmol glucose/1, but galactose, 3-O-methylglucose and α-methylglucoside (100 mmol/1 of each) produced significantly lower GIP responses than did glucose (P <0·02). Addition of 5 mmol phloridzin/1 to a perfusate containing 50 mmol glucose/1 prevented intestinal absorption of glucose and abolished the GIP response.

The molecular configuration of monosaccharides which have the ability to stimulate GIP release agreed well with the structural requirements for active transport by the sodium-dependent hexose pathway.
SHEDDING OF SURFACE PROTEINS BY PORCINE THYROID CELLS
Authors: BRENNAN A. , POVEY P. M. , REES SMITH B. , HALL R.
Published: December 2008

Isolated porcine thyroid cells were surface-labelled with 125I using the lactoperoxidase technique. Samples of the cells were then cultured and harvested at various intervals for up to 7 days. The labelled proteins remaining on the cells or shed into the culture medium were analysed by electrophoresis on polyacrylamide gels run in sodium dodecyl sulphate. These studies indicated that the several different surface proteins of the thyroid cells were lost from the cell surface at similar rates (half-time of approximately 28 h) as the result, at least in part, of a process which depended on active cell metabolism. In addition, the gel profiles obtained from analysis of both medium and membrane-bound labelled proteins were similar and this suggested that peptide cleavage was not involved in the shedding of the majority of these proteins.
ROLE OF THE GONADS IN THE REGULATION OF SEBACEOUS GLANDS IN RATS: COMPARISON OF THE EFFECTS OF CASTRATION AT AND AFTER BIRTH
Authors: TOH YEE CHU
Published: December 2008

Sprague–Dawley rats were castrated either within 24 h of birth or at 4 weeks of age. Control animals were sham operated. Intact female rats were also included for comparison. Sebum production was assessed at 80 days of age by measuring the amount of skin-surface lipids that could be extracted with acetone and which had been produced during 2 days.

The removal of the testes at birth reduced the activity of the sebaceous glands to a level more nearly approaching that seen in the female rats whereas castration at 4 weeks of age only partially decreased the rate of sebum secretion so that it was intermediate between the male and female rats. The weights of the pituitary gland, thyroid and adrenal glands increased after castration but there were no differences between rats castrated at birth and those castrated at 4 weeks of age except in the weight of the thyroid gland.

It would appear that the role of the testes in the control of the activity of the sebaceous glands is a sequential event which has already started at birth.
EFFECTS OF NALOXONE ON LUTEINIZING HORMONE AND PROLACTIN IN SERUM OF RATS
Authors: BLANK M. S. , PANERAI A. E. , FRIESEN H. G.
Published: December 2008

The effects of subcutaneous injections of the opiate antagonist naloxone on the tonic and phasic secretion of prolactin and LH were studied in rats. During development, resting levels of prolactin in serum were decreased by naloxone (2·5 mg/kg body wt) on days 24,45 and 50 in female rats and on days 28,45 and 50 in male rats. In the adult, naloxone (2·5 mg/kg body wt) decreased basal levels of serum prolactin in male rats and levels during oestrus in female rats. In 25-day-old female rats, serum LH rose from resting levels within 7·5 min of naloxone administration (2·5 mg/kg body wt) and returned to pretreatment levels by 30 min, while prolactin fell by 7·5 min and remained low for as long as 60 min after treatment. Furthermore, a tenfold lower dose of naloxone (0·25 mg/kg body wt) did not raise basal levels of serum LH but still decreased resting levels of serum prolactin in immature female rats (24 days old). The effect of naloxone (2·5 mg/kg body wt) on phasic LH release was studied in 29-day-old immature female rats primed on day 27 with pregnant mare serum gonadotrophin (PMSG). In these PMSG-treated rats the onset of the prolactin surge was blunted by naloxone while it had no effect on phasic LH release.

Naloxone (5 mg/kg body wt) also induced a rise in levels of serum LH in ovariectomized rats and, if administered with morphine, it reversed the short-term inhibition of LH secretion caused by morphine. However, naloxone was ineffective after pretreatment with oestradiol benzoate. These findings suggest that the responses of serum LH and prolactin to naloxone were dissociated and that oestrogens and opiate peptides may have interacted to regulate secretion of LH.
NEONATAL TREATMENT WITH ANTIOESTROGEN INCREASES THE DIURNAL RHYTHMICITY IN THE SEXUAL BEHAVIOUR OF ADULT MALE RATS
Authors: SÖDERSTEN P. , ENEROTH P.
Published: December 2008

Male rats were given daily injections of the antioestrogen ethamoxytriphetol (MER-25, 100 μ/day) or oil during the first 10 days of life. Rats treated with MER-25 showed a more pronounced diurnal rhythm in both mounting behaviour and lordosis behaviour than did oil-treated rats when tested as intact adults and after castration together with treatment with testosterone- or oestradiol-filled constant release implants. Serum levels of androgen varied markedly in samples obtained at four different times of the light: darkness (LD) cycle in both neonatal treatment groups and no significant LD-dependent pattern was obvious. Castration and treatment with testosterone implants produced stable androgen levels which showed little individual variation and did not vary with the LD cycle. The results supported the hypothesis that perinatal androgen stimulation affects the development of sexual behaviour in rats primarily by decreasing the diurnal rhythmicity of the behaviour of the adult.
AN ASSAY FOR RNA POLYMERASE ACTIVITY IN RAT BRAIN NUCLEI: EFFECTS OF INJECTION OF OESTRADIOL BENZOATE
Authors: GREENSTEIN B. D.
Published: December 2008

A sensitive, reliable assay of activity of RNA polymerase in purified nuclei from the rat brain is described. The assay measured the incorporation of [3H]guanosine triphosphate into RNA by nuclei. Little incorporation occurred in the presence of α-amanitin (400 ng) suggesting that RNA polymerase B activity was being measured. Preliminary evidence showed that after administration of oestradiol benzoate to 18-day-old female rats RNA polymerase activity was raised in areas of brain known to contain oestrogen receptors.
SUPPRESSION OF CONCENTRATION OF ENDOMETRIAL PROSTAGLANDIN IN EARLY INTRA-UTERINE AND ECTOPIC PREGNANCY IN WOMEN
Authors: ABEL MARGARET H. , SMITH S. K. , BAIRD D. T.
Published: December 2008

Concentrations of prostaglandin F2α (PGF2α) and prostaglandin E (PGE) were measured in endometrium from 18 women with ectopic pregnancies. In the nine pregnancies not associated with vaginal bleeding or an intra-uterine contraceptive device (IUCD; intact ectopics), concentrations of PGF2α (12·8 ± 7·4 (s.e.m.) ng/g) and PGE (4·7 ± 3·0 ng/g) were similar to those in decidua from nine intra-uterine pregnancies of comparable gestational age (14·4 ± 4·4 and 8·2 ± 2·2 ng/g respectively). In both ectopic and intra-uterine pregnancies concentrations of prostaglandins were significantly lower than those found in endometrium throughout the normal menstrual cycle (P < 0·01). In nine ectopic pregnancies with associated vaginal bleeding and/or an IUCD, concentrations of PGF2α and PGE were significantly higher than in the intact group (P < 0·05), although the concentration of PGF2α remained significantly lower than levels in normal secretory endometrium (P < 0·05).

These results suggested that suppression of endometrial synthesis of prostaglandin during early pregnancy may be mediated systemically rather than through a local action of the conceptus.
CYCLIC AMP LEVELS IN PURIFIED RAT ADRENAL ZONAE FASCICULATA AND RETICULARIS CELLS AND THE EFFECT OF ADRENOCORTICOTROPHIC HORMONE
Authors: HYATT P. J. , WALE L. W. , BELL J. B. G. , TAIT J. F. , TAIT S. A. S.
Published: December 2008

Cyclic AMP levels were measured in combined cells and supernatant fraction from incubations of dispersed rat adrenal zona fasciculata and zona reticularis cell preparations purified by unit gravity sedimentation. These measurements were correlated with deoxycorticosterone (DOC) and corticosterone outputs from the cells in the presence or absence of ACTH.

Similar measurements of cyclic AMP outputs were made for unpurified dispersed, decapsulated rat adrenal cell preparations and they were found to correspond to previously reported measurements made by other workers on such preparations.

The response of the purest zona reticularis cells to ACTH in terms of cyclic AMP output was 28-fold lower than that of the purest zona fasciculata cells (compared with a fivefold lower DOC output and a 20-fold lower corticosterone output) and the response to ACTH of the mixed-cell preparations was related to the number of zona fasciculata cells in the preparation, i.e. the greater the proportion of zona fasciculata cells in the preparation the greater the response in terms of both outputs of cyclic AMP and of either of the two steroids measured. This correlation is in accordance with the theory that cyclic AMP may be the secondary messenger for both zona fasciculata and zona reticularis cells of the rat adrenal cortex in mediating the response to an ACTH stimulus.
ABNORMALITIES IN THE SEASONAL COURSE OF OESTROUS CYCLES IN EWES AFTER LESIONS OF THE SUPRACHIASMATIC AREA OF THE HYPOTHALAMUS
Authors: PRZEKOP F. , DOMAŃSKI E.
Published: December 2008

The effects of lesions of the suprachiasmatic nuclei (SCN), anterior hypothalamic area (AHA) above the SCN and medial basal hypothalmus (MBH) on oestrous cycles in Merino ewes were observed. Ten animals with lesions of the SCN area continued to have oestrous cycles and ovulations throughout the whole breeding season; in six of these ewes the cycles and ovulations did not stop but were extended into the quiescent non-breeding period. Lesions placed above the SCN in the AHA (three animals) did not affect the oestrous cycles. Together with earlier experiments involving anterior hypothalamic deafferentation rostral and caudal to the SCN, it is suggested that the SCN has a role in transmitting inhibitory action from the medial preoptic area and suppressing the liberation of gonadotrophin-releasing hormone(s) (GnRH) during the non-breeding anoestrous period.

Injury to the MBH was followed by cessation of oestrous cycles and of ovulation, a decrease in the number and size of gonadotrophic cells, atrophy of the ovaries and a lowered basal concentration of LH in plasma. This was probably the result of injury to the neurones that produce or transport GnRH to the median eminence.
CLOMIPHENE AND TAMOXIFEN ACTION IN THE RAT UTERUS
Authors: KURL R. N. , BORTHWICK N. M.
Published: December 2008

The antioestrogens clomiphene and tamoxifen exhibit both agonistic and antagonistic properties in the rat uterus. The effect of these antioestrogens on RNA polymerase activities in the rat uterus was investigated. Both compounds stimulated an early increase in the activity of endogenous RNA polymerase B similar to that observed after oestradiol treatment. A secondary stimulation of activity of RNA polymerase B was observed after treatment with oestradiol and both antioestrogens. In addition, the activity of endogenous RNA polymerase A was increased initially at 1 h by all three compounds but this activity was maintained at 24 h only by oestradiol.
STABILITY OF THE THIRD INTERNATIONAL STANDARD FOR CORTICOTROPHIN: ACCELERATED DEGRADATION STUDY USING DIFFERENT BIOASSAYS AND ISOELECTRIC FOCUSING
Authors: STORRING P. L. , GAINES-DAS ROSE E. , TIPLADY R. J. , STENNING BRIDGET E. , MISTRY Y.
Published: December 2008

The corticotrophin activity of ampoules of the Third International Standard for Corticotrophin (IS) kept at 20 and 37 °C for 15 years was compared with that of ampoules of the IS stored under normal conditions (−20 °C in the dark), using adrenal ascorbate depletion assays after subcutaneous administration of the hormone, assays of an increase in plasma corticosterone after intravenous administration of the hormone and in-vitro adrenal cell corticosterone production assays. Estimates of activity by all three methods are homogeneous and give combined weighted geometric means (with 95% confidence limits), as per cent of the activity in the IS stored at −20 °C, of 92·1 (84·8–100) and 77·8 (71·6–84·5) for the 20 and 37 °C degradation samples respectively.

Isoelectric focusing studies of the ampoule contents of the three preparations showed that ampoules of the IS stored at 20 and 37 °C contained 90 and 79% respectively, of the component representing native corticotrophin found in the IS. These estimates of corticotrophin content are comparable to the estimates of biological activity of these preparations.

The stability of the IS was calculated from the combined bioassay data assuming that degradation follows first order kinetics. The predicted half-life for the activity of the IS is 2800 years with an approximate lower 95% confidence limit of 500 years; the predicted activity of the IS remaining now, after 20 years at −20 °C, is 99·5% of the original activity with an approximate lower 95% confidence limit of 97·3%