bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF PROSTAGLANDIN F2α ON PROGESTERONE, OESTRADIOL AND LUTEINIZING HORMONE SECRETION IN SHEEP WITH OVARIAN TRANSPLANTS
Authors: CHAMLEY W. A. , BUCKMASTER JOAN M. , CAIN M. D. , CERINI J. , CERINI MILDRED E. , CUMMING I. A. , GODING J. R.
Published: December 2008

The luteolytic properties of prostaglandin F2α (PGF2α) were studied in experiments on sheep with ovarian autotransplants. PGF2α was infused at the rate of 40, 10 and 2 μg/h for 4·0, 7·0 and 9·5–18·0 h respectively. At rates of 40 and 10 μg/h, progesterone secretion decreased to 50% of the control levels in 2·6 ± 1·4 h and fell to 8–30 μg/h within 36–52 h from the start of infusion. The onset of oestrus occurred 42–66 h after the infusions had started and a typical pre-ovulatory surge of luteinizing hormone (LH) was observed 52–66 h after infusing PGF2α. On occasions, this surge was accompanied by a brief peak of oestradiol-17β secretion and shortly thereafter ovarian steroidogenesis decreased to very low levels.

In four sheep infused at a rate of 2 μg/h, peripheral progesterone values decreased gradually and only one animal returned to oestrus. It would seem that 2 μg/h is close to the minimum intra-arterial dose to cause luteolysis in the sheep.
SOME ASPECTS OF THE CONTROL OF DEHYDROEPIANDROSTERONE SYNTHESIS IN THE HUMAN ADRENAL GLAND IN VITRO
Authors: JENSEN VIBEKE , CARSON PAMELA , DESHPANDE N.
Published: December 2008

The control of dehydroepiandrosterone (DHA) synthesis in the human adrenal gland was studied by investigating the biosynthesis of its immediate precursor, 17-hydroxypregnenolone (3β,17α-dihydroxy-pregn-5-en-20-one) and the side-chain cleavage. Both conversions take place in the microsomal fraction and there is an obligatory requirement for the co-factor, reduced nicotinamide adenine dinucleotide phosphate (NADPH). Under optimal conditions, 17-hydroxylation is controlled only by the availability of the substrate and the co-factor. By using the same kinetic approach it was observed that the synthesis of DHA is controlled by the availability of substrate and co-factor. However, the reaction was inhibited by the oxidized form (NADP+) and when the ratio of NADP+:NADPH reached 1, the maximum velocity was halved.

Two major metabolites of 17-hydroxypregnenolone, namely DHA and 17-hydroxyprogesterone, are non-competitive inhibitors of the reaction. The inhibition constants are of the magnitude of the tissue concentration of these steroids in the adrenal gland which suggests that non-competitive inhibition takes place in vivo.
THE LOCALIZATION OF PROLACTIN LABELLED WITH RADIOACTIVE IODINE IN RABBIT MAMMARY TISSUE
Authors: BIRKINSHAW MARGARET , FALCONER I. R.
Published: December 2008

Study of the removal of 125I-labelled prolactin from the blood of virgin oestrous, pseudopregnant, lactating, weaned and post-partum oestrous rabbits gave a mean half-life of 16·0 ± 1·54 min. No conclusions could be drawn from the results on the influence of physiological condition on half-life. Tissue distribution of 125I-labelled prolactin 60 min after i.v. injection showed that the highest uptake ratio of tissue: plasma was in the kidney, which was confirmed with a concentration of 125I in the urine 6·43 times higher than in the plasma. However, approximately 90% of the 125I in the urine was in the form of labelled products of prolactin degradation. The uptake ratio of mammary tissue: plasma was 2·40 ± 0·09:1 during lactation but was only 0·41 ± 0·04:1 in oestrous rabbits. Of other tissues liver showed the highest ratio of 0·85 ± 0·03:1. The half-life of both 125I- and 131I-labelled prolactin was investigated in vivo in mammary tissue, after i.v. or intraductal injection. No significant differences were seen between methods of administration or differences of isotope, and the average half-life was 52·4 ± 5·9 h.

Autoradiographic studies of the tissue localization of 125I- and 131I-labelled prolactin were carried out, the hormone being administered by i.v. or intraductal injection to 15-day pseudopregnant rabbits, or by incubation with 0·5 mm slices of lactating mammary tissue from rabbits. Samples of tissue were obtained from 10 min to 50 h after administration of labelled hormone. Irrespective of method of administration, isotope or time interval, a selective localization of radioactivity was observed on or near to the alveolar secretory cell membrane, on the side adjacent to the vascular supply. It was concluded that specific sites for labelled prolactin occur in this location, since the opposite side of the alveolar cell membrane adjacent to the duct lumen did not show radioactivity localized on or near it, even when the hormone was administered into the teat ducts.
BIOSYNTHESIS OF HUMAN CHORIONIC GONADOTROPHIN IN VITRO: INCORPORATION OF [14C]l-LEUCINE
Authors: BENAGIANO G. , PALA A. , MEIRINHO M. , ERMINI M.
Published: December 2008

Fresh human placental tissue from first trimester pregnancies was incubated with [14C]l-leucine and the incorporation of the labelled amino acid into placental proteins was studied in both the soluble and the particulate fractions. Free [14C]l-leucine was completely separated from labelled proteins by exhaustive dialysis. This was confirmed by Sephadex G-100 gel chromatography.

In preliminary experiments, the total protein fraction from Sephadex was submitted to polyacrylamide gel electrophoresis; columns divided into ten sections were checked, fraction by fraction, for incorporated radioactivity and human chorionic gonadotrophin (HCG) potency, using a radioimmunoassay method. In all instances, the highest HCG activity corresponded to the highest incorporation of radioactivity. In subsequent experiments only those radioactive proteins were used which had the highest activity after chromatography. This peak was further divided into two parts which were submitted to polyacrylamide gel electrophoresis. Using the ascending limb of the peak which contained about 70% of the total HCG activity, there was complete agreement between the distribution of radioactivity and that of HCG activity, whereas the bulk of HCG radioimmunological activity in the descending limb could be dissociated from radioactive proteins.

After absorption of the HCG-like protein with specific anti-HCG serum, HCG activity was completely neutralized and more than 95% of the corresponding radioactivity disappeared. Additional evidence for the presence of an HCG-like biosynthesized protein was obtained after DEAE-cellulose ion exchange chromatography of the products of the incubation. Here again, the HCG potency of the radioactive protein with the highest activity was completely neutralized after absorption with a specific antiserum: in this case, however, only some 60% of the total radioactivity present disappeared after absorption.

The results indicate that human placental tissue can synthesize from l-leucine proteins possessing radioimmunological HCG activity.
ANDROGEN DYNAMICS IN VITRO IN THE CANINE PROSTATE GLAND
Authors: GIORGI ELEONORA P. , GRANT J. K. , STEWART JOAN C. , REID JACQUELINE
Published: December 2008

The uptake and metabolism of androgens by canine prostate in vitro were studied by means of an experimental design which consisted of superfusion of prostate slices with a medium containing [4-14C]androstenedione and [6,7-3H]testosterone, or [4-14C]testosterone and 5α-dihydro[1,2-3H]testosterone. The entry or transfer of steroids into the slices, the irreversible metabolism, the conversion between the steroids and their uptake or tissue retention were measured at the steady state. A similar proportion of the three androgens entered the tissue and was irreversibly metabolized. Conversion of testosterone into 5α-dihydrotestosterone was much greater than the interconversion of testosterone and androstenedione. The prostate slices retained 5α-dihydrotestosterone in a concentration up to four times that in the medium, whereas testosterone and androstenedione were retained to a smaller extent.

By increasing the steroid concentration in the perfusing medium from 0·03 to 1·30 μmol/l, it was shown that the systems regulating entry, uptake and metabolism of the androgens were not saturated within this range of concentration. No substantial differences were observed in the regulation of tissue—androgen interaction in vitro between five normal and four hyperplastic canine prostates. This was in contrast with previously reported findings that, in man, normal and hyperplastic prostatic tissue respond in a different way to an increase in steroid concentration in the medium.
CELL DIVISION AND DNA SYNTHESIS IN THE MOUSE UTERUS DURING CONTINUOUS OESTROGEN TREATMENT
Authors: LEE AUDREY E.
Published: December 2008

Continuous oestrogen stimulation produced an initial increase in mitosis and [3H]thymidine incorporation in the mouse uterine luminal epithelium on days 2 and 3 of treatment, but activity fell to the level of the untreated uterus on days 4 and 5. The implications of this control of cell division are discussed. A second wave of activity occurred about a week later, and in the longest experiment a third wave was seen on days 19 to 21. This pattern was similar to that seen in the glandular epithelium. There was little cell division in the stroma or myometrium. The rhythm was not due to diurnal variation. It was seen after treatment with oestrone and oestradiol, given either by injection or in the drinking water.
THE EFFECT OF GONADOTROPHINS ON FLUID SECRETION AND SPERM PRODUCTION BY THE RAT AND HAMSTER TESTIS
Authors: SETCHELL B. P. , DUGGAN M. C. , EVANS R. W.
Published: December 2008

Single intravenous injections of ovine luteinizing hormone (LH) in adult hamsters and rats had no effect on fluid secretion by the testes, as measured by the gain in weight or water content during a 10-h period after ligation of the efferent ducts (EDL). Neither was there any obvious effect on the liberation of spermatozoa, as judged by the total number of sperm in the unligated and EDL testes and from the concentration of spermatozoa in the secreted fluid, calculated from the difference between the number of sperm in the EDL and unligated testes divided by the difference in weight.

In adult rats treated for 9 weeks with human chorionic gonadotrophin and/or pregnant mare serum gonadotrophin, there was a decrease in sperm production (measured as described above during a 20-h period after EDL) when the two hormones were given together. These treatments, continued for 3 or 9 weeks, had no effect on testicular weight, nor on the secretion of fluid, and the two hormones given together for 9 weeks caused a decrease in the concentration of sperm in collected rete testis fluid. The concentration of spermatozoa in collected rete testis fluid was about one quarter of the calculated concentration in the total secreted fluid.

Ovine follicle-stimulating hormone (FSH) injected daily for 3 days in 21-day-old rats stimulated fluid secretion slightly, and FSH +ovine growth hormone stimulated fluid secretion by the testes of adult rats with oestrogen implants. Ovine LH caused a slight decrease in fluid secretion in oestrogen-treated adults and also in the 21-day-old rats. Ovine prolactin and growth hormone had no significant effect on fluid secretion by the testis in these two groups of rats.
EFFECTS OF OVARIAN STEROID HORMONES ON HISTOCHEMICALLY DEMONSTRABLE LIPIDS IN THE RAT UTERINE EPITHELIUM
Authors: BOSHIER D. P. , HOLLOWAY HILARY
Published: December 2008

Histochemical studies showed that during the rat oestrous cycle, uterine epithelial lipids were at their highest levels during dioestrus and pro-oestrus. In ovariectomized mature animals given oestradiol-17β, either by itself or in combination with medroxyprogesterone acetate, neutral lipids and unsaturated lipids were below control levels, while phospholipids were increased. Medroxyprogesterone acetate, however, increased levels of neutral lipids and unsaturated lipids, and decreased phospholipids. It is suggested that during the oestrous cycle of the rat, high concentrations of uterine epithelial lipid during late dioestrus and pro-oestrus reflect the increased plasma progesterone of early dioestrus acting in a low plasma oestrogen environment.
METABOLIC STUDIES IN A PATIENT WITH A PHAEOCHROMOCYTOMA ASSOCIATED WITH HYPOKALAEMIA AND HYPERALDOSTERONISM
Authors: WILSON R. J. , CRAIG GILLIAN M. , MILLS I. H.
Published: December 2008

A case of phaeochromocytoma with hypokalaemia, hyperaldosteronism, normal cortisol production and normal urinary corticosteroid excretion is described. Both α-adrenergic blockade and combined α and β blockade resulted in marked antidiuresis with urinary sodium and potassium retention and a rise in plasma volume. Combined α and β blockade led to some reduction in the high aldosterone production rate. The hypokalaemia was corrected by α-adrenergic blockade. After operative removal of the tumour the aldosterone production rate was normal.

The marked reduction in urinary sodium excretion in response to α-adrenergic blockade, if reproducible in other cases of phaeochromocytoma, might be a useful test for the presence of a phaeochromocytoma.
INHIBITION OF MILK SECRETION BY INTRAPERITONEAL INJECTIONS OF MILK INTO LACTATING MICE
Authors: SALA N. L. , CANNATA M. A. , LUTHER E. , ARBALLO J. C. , TRAMEZZANI J. H.
Published: December 2008

The effect of milk reabsorption upon lactation was studied by giving daily intraperitoneal injections of milk to lactating mice during the first 5 days of lactation.

The weight gain of the young of mice injected with mouse or cow milk was similar but was less than the gain of the young of the non-injected control mice. The weight gain of the young of the mothers receiving lipid-free cow milk was similar to that of the controls, whereas that of the young of mothers receiving lipid-free cow milk with added lipids was again less than in the control group. There was no difference in litter mortality rate between the controls and the group treated with lipid-free cow milk, nor between the groups treated with mouse, cow and lipid-free cow milk with added lipids; the mortality, however, in the three latter groups was higher than in the two former ones. The injection of milk decreased milk yield. The effect of the injection of milk was observed within 24 h of the first injection.

The results suggest that milk secretion is impaired by the injection of milk. The effect may be ascribed to the lipid fraction of milk or to some unknown chemical factor within it. The rapid onset of the effect suggests that it is not mediated by an immunological reaction.
THE PROGESTERONE CONCENTRATIONS IN THE PERIPHERAL PLASMA OF THE MINK (MUSTELA VISON) DURING PREGNANCY
Authors: MØLLER O. M.
Published: December 2008

In mink bitches mated once, the progesterone levels in plasma remained at the basal level (< 8 ng/ml, i.e. comparable with the progesterone levels in anoestrous mink) during the first days after coitus. The duration of this lag period varied from 10 to about 20 days, and was found to correspond with the length of gestation. However, in general a gradual increase was observed beginning about 40 days before parturition with a maximum plasma progesterone concentration (63–105 ng/ml) from 10 to 25 days later on. After the peak value had been attained the plasma progesterone concentration declined gradually to the day of parturition and was low ( < 10 ng/ml) at parturition and afterwards. The progesterone values and profiles obtained from females mated twice corresponded with those obtained from females mated once. The increase in progesterone, however, began a few days after the second mating.

The developmental stages of the foetuses corresponded clearly with the progesterone profile.

In three mated females which failed to give birth a slow increase in progesterone concentration was observed beginning about 15 days post coitum. In these bitches the progesterone concentration reached a plateau (30–45 ng/ml) between day 30 and day 40 post coitum, after which a slow decline was observed. The period when the progesterone concentrations were increased above the basal level lasted about 40 days even in the females which did not give birth.
EFFECT OF OESTROGEN UPON PARTURITION, MATERNAL BEHAVIOUR AND LACTATION IN OVARIECTOMIZED PREGNANT RATS
Authors: CATALÁ SILVIA , DEIS R. P.
Published: December 2008

Ovariectomy of rats on day 20 of pregnancy impaired parturition and lactation. All rats showed prolonged delivery with many foetuses born dead and the mothers were unable to rear the young. Treatment with oestradiol benzoate (0·5 or 1 μg) in a single dose permitted normal delivery and lactation when the hormone was injected immediately after ovariectomy. Oestrogen administered the day after ovariectomy was not effective. The administration of prolactin and corticotrophin to ovariectomized pregnant rats did not prevent abnormal parturition but lactation improved in 50% of the mothers. A group of animals ovariectomized on day 20 was treated with oxytocin every 2 h on day 22 starting at 08.00 h. This treatment did not facilitate parturition and lactation. Maternal behaviour, which was always present in the other groups, was also impaired by this treatment. When ovariectomy was performed on the evening of day 21 of pregnancy, a partial impairment of parturition was observed but lactation was normal in seven out of eight rats. The results indicate that oestrogen is essential near term for normal parturition and lactation. The absence of the steroid may make the uteri less sensitive to oxytocic substances and also affect milk ejection.
FURTHER STUDIES ON CHOLINERGIC MECHANISMS AND HORMONE-ACTIVATED COPULATORY BEHAVIOUR IN THE FEMALE RAT
Authors: LINDSTRÖM L. H.
Published: December 2008

Previous experiments have demonstrated that the cholinergic compounds pilocarpine and oxotremorine decrease the oestrogen plus progesterone-activated lordosis response in the female rat. The present study showed that pilocarpine and oxotremorine, in doses which did not interfere with overt behaviour, also facilitated the lordosis response when given 48 h after oestrogen and thus substituted for the progesterone treatment. This effect could be counteracted by atropine but not by methylatropine pretreatment. The facilitating effect was not obtained after adrenalectomy or hypophysectomy. It is therefore suggested that the facilitating effects of the cholinergic compounds on copulatory behaviour in the oestrogen-treated female rat is mediated by pituitary—adrenal mechanisms.
ANDROGEN-DEPENDENT SYNTHESIS OF α2u GLOBULIN IN THE RAT: ROLE OF THE PITUITARY GLAND
Authors: ROY A. K.
Published: December 2008

Hypophysectomy completely abolished the androgen-dependent synthesis of α2u globulin in adult rats. Experiments with adrenalectomized and thyroidectomized adult male rats showed that these endocrine ablations also reduced the daily urinary output of α2u globulin to about 10% or less than those of the pre-operative values. The effects of adrenalectomy and thyroidectomy on α2u output could be reversed to normal with the supplementation of corticosterone and thyroxine respectively. However, none of the pituitary hormones administered alone or along with testosterone was able to reverse the effect of hypophysectomy. Simultaneous treatment with growth hormone, corticosterone and thyroxine along with testosterone was required for the complete reversal of the effect of hypophysectomy. It is concluded that the androgenic induction of α2u globulin is dependent on the synergistic effects of growth and developmental hormones such as growth hormone, thyroxine and corticosterone.
A COMBINED BIOCHEMICAL AND HISTOLOGICAL STUDY ON THE ISLETS OF LANGERHANS IN THE GENETICALLY OBESE HYPERGLYCAEMIC MOUSE AND IN THE LEAN MOUSE, INCLUDING OBSERVATIONS ON THE EFFECTS OF STREPTOZOTOCIN TREATMENT
Authors: FINDLAY J. A. , ROOKLEDGE K. A. , BELOFF-CHAIN ANNE , LEVER J. D.
Published: December 2008

The biochemical parameters of blood glucose, serum insulin and pancreatic insulin and glucagon were determined after single injections of the diabetogenic agent streptozotocin and in untreated animals from a strain of genetically obese mice and their lean litter-mates. Histological observations on α and β islet cells were also made in these animals by employing the phosphotungstic acid—haematoxylin and aldehyde—fuchsin staining techniques.

In untreated obese mice, endocrine hyperactivity was indicated by the presence of exceptionally large, highly vascular islets and by duct cell-islet metaplasia.

After streptozotocin injection, approximately half of the lean mice showed extensive β-cell necrosis and these animals became hyperglycaemic and hypoinsulinaemic with a much reduced pancreatic insulin over a long term. The remaining treated lean mice, whose biochemical parameters did not differ significantly from normal, showed little or no evidence of islet damage. The response of obese mice to streptozotocin treatment was less clear-cut than that of lean animals. Essentially similar histological changes were observed, though these were not consistently correlated with biochemical data. There was histological and biochemical evidence of islet cell recovery from the effects of the drug both in lean and in obese mice, and in all hyperglycaemic animals with initial severe islet damage a marked α-cell response was observed, namely an increased proportion of α cells and their random deployment throughout the islets.
THIOCYANATE ION IN SERUM AS AN INTERFERING FACTOR IN THE IN-VITRO BIOASSAY OF THYROTROPHIN
Authors: BOURKE J. R. , MANLEY S. W. , HAWKER R. W.
Published: December 2008

The presence of thiocyanate ion in human and rat serum has been shown to account entirely for the non-specific activity of sera in an in-vitro bioassay for thyrotrophin. Thiocyanate was identified by its chromatographic behaviour on Sephadex G-10, G-15 and G-25, and by the ferric nitrate and cobalt nitrate tests. Cigarette smoking increased mean serum thiocyanate levels (as NaSCN) from 0·2 to 0·56 mg/100 ml. It is suggested that serum thiocyanate levels are sufficient to inhibit significantly iodide trapping in vivo and that these findings may be relevant to the non-specific responses observed with other in-vitro bioassays based on radioiodine dynamics.
EFFECT OF DECAPITATION ON THE DEVELOPMENT OF INSULIN SECRETION IN THE FOETAL RABBIT
Authors: JACK P. M. B. , MILNER R. D. G.
Published: December 2008

One rabbit foetus in a litter was decapitated on day 24 of gestation. On day 29 the litter was killed and blood was collected from all foetuses for the measurement of plasma insulin concentration. The pancreas of the decapitated foetus and that of the control litter-mate with the nearest headless body weight were cut into pieces and incubated in a physiological buffer containing 0·6 or 3·0 mg glucose/ml. The pancreas of the decapitated foetus secreted significantly more insulin than that of the control foetus in either concentration of glucose in the medium. Higher insulin secretion from the decapitated foetus persisted for 4·5 h of incubation and was demonstrable in both the first 5 and subsequent 25 min of incubation when the pancreas was initially transferred to incubation medium containing 3·0 mg glucose/ml. The mean plasma insulin concentration of the foetuses decapitated on day 24 was higher on day 29 than that of the control foetuses but there was no significant difference between the concentration of insulin in the pancreas of the two groups of animals. The results indicate that removal of the foetal head influences the intrauterine development of the rabbit β-cell.
HORMONAL SPECIFICITY IN THE SUPPRESSION OF SEXUAL RECEPTIVITY OF THE FEMALE GOLDEN HAMSTER
Authors: CONIGLIO LINDA P. , PAUP D. C. , CLEMENS L. G.
Published: December 2008

Oestrogen—progesterone-induced lordosis behaviour was suppressed in female hamsters which received neonatal treatment with testosterone propionate or diethylstilboestrol. No suppression of lordosis was observed in females which received neonatal treatment with testosterone, androsterone or control substances. In addition, the ano—genital distance and diameter of the vaginal orifice were increased in females treated with testosterone, testosterone propionate, androsterone or diethylstilboestrol. However, testosterone, testosterone propionate and androsterone had a greater effect on ano—genital distance than did diethylstilboestrol. Possible mechanisms for the defeminizing action of the hormones administered were discussed.
VASOPRESSIN AND MILK SECRETION: LACK OF EFFECT OF LOW DOSES
Authors: PEAKER M. , LINZELL J. L.
Published: December 2008

The infusion of vasopressin in amounts thought to be released during water deprivation had no effect on the rate of milk secretion or on milk composition. These results do not support the conclusions of Konar & Thomas (1970) that vasopressin at physiological levels affects the rate of milk secretion, since the doses they used were very much higher and probably outside the physiological range. The implications of these findings and their possible adaptive significance are discussed.
THE METABOLISM OF TESTOSTERONE BY HUMAN MALE SCALP SKIN
Authors: BINGHAM K. D. , SHAW D. A.
Published: December 2008

[4-14C]Testosterone was incubated with human male scalp skin and the metabolites identified as 5α-androstane-3α, 17β-diol, androsterone, epiandrosterone, dihydrotestosterone, androstenedione and androstanedione. A metabolite not previously reported from incubations of human skin with androgens was isolated and is probably a steroid ester.

One bald and one hairy scalp biopsy specimen from each of five subjects were incubated with [4-14C]testosterone for 1 h and the radioactivity of each metabolite was measured after separation by thin-layer chromatography. Both the uptake and metabolism of testosterone were greater in bald skin than in hairy skin. Little difference in the percentage of each metabolite in the total metabolite pool was found between bald and hairy skin from the same subject and skin from different subjects. This demonstrated that male pattern baldness was not accompanied by gross changes in testosterone metabolism. The main finding was that bald skin contained increased amounts of 5α-reduced metabolites.
URINARY PREGN-5-ENE-3α, 16α,20α-TRIOL IN ADRENAL DYSFUNCTION
Authors: FANTL VERA , BOOTH MOLLIE , GRAY C. H.
Published: December 2008

Pregn-5-ene-3α, 16α,20α-triol in amounts from 50 to 220 μg/24 h was found in the urine of normal adult men and women. Excretion within this range was also found in five adult women of whom two had congenital adrenal hyperplasia, one had Cushing's disease, one was hirsute and infertile and one was obese. Except for one patient, who excreted amounts within the normal range, subjects with adrenal carcinoma excreted up to 15 mg of this steroid/24 h.
THE STIMULATION BY PROLACTIN AND GROWTH HORMONE OF FATTY ACID SYNTHESIS IN EXPLANTS FROM RAT MAMMARY GLANDS
Authors: HALLOWES R. C. , WANG D. Y. , LEWIS D. J. , STRONG C. R. , DILS R.
Published: December 2008

Explants of mammary glands and of subcutaneous body fat from sexually mature virgin and from 19-day pregnant Sprague-Dawley rats and of mammary gland from 5-day lactating Sprague-Dawley rats, were maintained in organ culture for up to 96 h. The effects of insulin (I), corticosterone (B), prolactin (P) and growth hormone (G) on the rate of fatty acid synthesis were measured by the incorporation of [14C]acetate. The effect of these hormones on the synthesis of various carbon-chain length fatty acids was measured by radio gas-liquid chromatography.

Explants from both tissues had a reduced rate of fatty acid synthesis after 24 h in medium 199, but this rate was increased by the addition of insulin. In explants of subcutaneous fat from virgin rats, the rate was further increased by culture in IBP or IBG, but this increase was not blocked by actinomycin D. In explants from subcutaneous fat of 10-day pregnant rats the rate was not increased by the addition of B, P or G to the insulin-containing medium. In mammary gland explants from virgin rats, IBP stimulated a greater rate of fatty acid synthesis than did insulin alone. In mammary gland explants from 10-day pregnant rats, the rate of fatty acid synthesis was increased by both IBP and IBG. In mammary gland explants from rats on the 5th day of lactation, both IBP and IBG increased the rate of fatty acid synthesis compared with insulin or IB. Actinomycin D blocked the increased fatty acid synthesis produced by prolactin or growth hormone but not that produced by insulin alone.

Mammary gland explants from rats on the 5th day of lactation were cultured for the first 4 h after excision in medium 199 that contained sodium [14C]acetate. Sixty-eight per cent of the 14C was incorporated into C8-C12 fatty acids. In explants from subcutaneous fat none of the hormones tested increased 14C incorporation in these fatty acids. In mammary gland explants from virgin or 10-day pregnant rats, insulin, corticosterone and prolactin increased the incorporation in these fatty acids. Growth hormone was less efficient than prolactin in stimulating C8-C12 fatty acid synthesis.
SOME EFFECTS OF THYROID DISEASE ON NEUTRAL STEROID METABOLISM
Authors: BEALE R. N. , CROFT D. , POWELL DENISE
Published: December 2008

Gas—liquid chromatography was used to compare the urinary levels of 18 neutral steroid metabolites in normal, hyper- and hypothyroid subjects. Numerous significantly abnormal parameters were observed in both disease states.

In hyperthyroidism the ratios of total androsterone: total aetiocholanolone and of their aglycones were increased. Total 17α-hydroxycorticosteroids were moderately increased largely because of augmented levels of some major metabolites, e.g. the summed cortolones, with only small decreases in others, e.g. tetrahydrocortisol. The percentage contribution of tetrahydrocortisol to its group of eight related metabolites was, however, profoundly reduced.

In hypothyroidism the excretions of all major glucosiduronates and sulphates of the 11-deoxy-17-oxosteroid group were greatly, and some profoundly, reduced, with a marked decrease in the ratio of the aglycones androsterone:aetiocholanolone. Total 17α-hydroxycorticosteroids were moderately decreased, largely because of low outputs of tetrahydrocortisone and of the summed cortolones. There was a profound decrease in the percentage contribution of 5α-tetrahydrocortisol.

Explanations of the observations are attempted in terms of hypothetical changes in the activities of certain steroid-metabolizing enzymes.
THE INFLUENCE OF EXTEROCEPTIVE STIMULI AND PHEROMONAL FACILITATION OF OVULATION IN DIFFERENT STRAINS OF MICE
Authors: ELEFTHERIOU B. E. , CHRISTENSON C. M. , ZARROW M. X.
Published: December 2008

Pheromonal facilitation of pregnant mare serum gonadotrophin (PMSG)-induced ovulation was compared in four strains of immature mice after exposure to adult intact males, castrated males, castrated males after treatment with testosterone propionate, or exposure to adult females. Psychobehavioural modification of their response was studied after transferring PMSG-injected females between cages, or after their exposure to either electric foot shock or adverse auditory stimuli. Significant facilitation of the average number of ova released and percentage of mice ovulating was found in females of the strains C3HeB/FeJ and BALB/cJ, but not in strains DBA/2J and C57BL/6J after exposure to adult males. Exposure to castrated males treated with testosterone propionate resulted in a response essentially the same as that to intact males, whereas exposure to adult females inhibited ovulation uniformly in all the strains studied except BALB/cJ. Auditory stimuli prevented this phenomenon in strains C3HeB/FeJ and C57BL/6J, but an obvious facilitation was observed in strains BALB/cJ and DBA/2J. Electric shock facilitated ovulation in strain DBA/2J but not in the other three strains.
CHARACTERIZATION OF THE SPECIFIC ANDROGEN RECEPTORS IN THE HUMAN PROSTATE GLAND
Authors: MAINWARING W. I. P. , MILROY E. J. G.
Published: December 2008

A search has been conducted for specific androgen-binding proteins in soluble extracts of normal human prostate tissue and in surgical samples removed at retropubic prostatectomy for benign prostatic hyperplasia. Proteins with a particularly high affinity for a metabolite of testosterone, 5α-dihydrotestosterone, have been identified in studies on the binding of 3H-labelled steroids in vitro. The 5α-dihydrotestosterone-protein complexes have been partially characterized using sucrose density gradient centrifugation and gel-exclusion chromatography. The androgen receptors in the human prostate gland are remarkably similar to those previously described in the accessory sexual glands of experimental animals. These findings have been confirmed by the analysis of extracts of hyperplastic prostate glands labelled by the administration of [3H]testosterone in vivo. No attempt was made to correlate the degree of binding with the histological appearance of the specimens of hyperplastic prostate or to determine whether the receptors were principally present in the hyperplastic nodules. Such androgen-binding proteins were not present in serum, skeletal muscle or adipose tissue. The possible relevance of these findings to the onset of clinical disorders in the human prostate gland is briefly discussed.
LABILITY OF HUMAN PITUITARY FOLLICLE-STIMULATING HORMONE TO MILD ACID TREATMENT
Authors: KENNEDY J. F. , CHAPLIN M. F.
Published: December 2008

The lability of human pituitary follicle-stimulating hormone (FSH) to dilute hydrochloric acid was studied. Hydrolysis at pH 1·0 and 20 °C for 3 h abolished the biological activity of the hormone in vivo, but hydrolysis at pH 0·0 and 20 °C for 3 h gave rise to fragments of low molecular weight which retained immunological activity. In contrast, the weakest hydrolysis conditions which removed all the N-acetylneuraminic acid units were pH 2·0 at 80 °C for 50 min. Under these conditions, 75% of the fucose units but none of the other monosaccharide units of FSH were liberated. The results demonstrate the considerable lability of FSH to mild acid and provide an example of a glycoprotein, acid hydrolysis of which is unsuitable for removal of N-acetylneuraminic acid and fucose units selectively.
THYROTROPHIN SECRETION FROM RAT PITUITARY AUTOGRAFTS INFUSED WITH SYNTHETIC THYROTROPHIN RELEASING FACTOR
Authors: AVERILL R. L. W. , EVANS J. S.
Published: December 2008

Thyroidal uptake and release of 131I were used to study the response of pituitary autografts to locally infused synthetic thyrotrophin releasing factor (TRF) and porcine median eminence extract (MEE). Thyroidal release rates of 14% 131I/24h were maintained during continuous infusion of grafts with MEE (equivalent to 4 hypothalami/day) while 12·6% 131I/24 h was lost from thyroids of rats whose pituitary autografts were infused with 1000 ng synthetic TRF/day. Infusion of autografts with 5, 50 and 250 ng synthetic TRF/day resulted in lower, but dose-dependent, thyroidal responses suggesting that synthetic TRF could induce thyrotrophin (TSH) synthesis in the grafts.

At all doses of TRF, thyroidal 131I release was significantly increased by daily injection of cortisone (2 mg s.c.).

Local TRF stimulation of TSH release from pituitary grafts significantly increased the dose of thyroxine (T4) needed to decrease thyroid activity, and while 1·0 μg T4/100 g depressed activity in rats receiving saline infusions, 1·7–2·7 μg T4/100 g was needed to inhibit 131I release in rats receiving 250 ng TRF/day, and 3 μg T4/100 g was needed by rats receiving 1000 ng TRF/day.

Continuous TSH infusion (25–28 mu./day) into hypophysectomized rats induced thyroidal 131I release at rates similar to those in rats with TRF-stimulated pituitary autografts.

It is suggested that while synthetic TRF can enhance TSH synthesis in the pituitary its effects on TSH synthesis may normally be potentiated by other humoral substances.
THE CONTROL OF ARGININE-INDUCED INSULIN SECRETION IN THE RAT: THE ROLE OF CATECHOLAMINES
Authors: BACCHUS R. A. , MEADE L. , HUTCHINSON J. S. M. , LONDON D. R.
Published: December 2008

The effect of alterations in catecholamine metabolism on arginine-induced insulin release was studied in the anaesthetized rat. Alpha-methyl-p-tyrosine, which inhibits catecholamine synthesis, guanethidine, which prevents catecholamine release, and reserpine, which depletes catecholamine stores, all enhanced the secretion of insulin and reduced the rise in blood glucose after the amino acid load. Adrenalectomy, with or without corticosterone replacement, had a similar effect. Adrenaline inhibited the insulin response to arginine. It was concluded that in the rat, adrenergic mechanisms modulate the insulin response to arginine.
THE EFFECTS OF HYPOPHYSECTOMY AND THE PARADOXICAL EFFECT OF HUMAN CHORIONIC GONADOTROPHIN ON THE VIABILITY OF HAMSTER SPERMATOZOA
Authors: LUBICZ-NAQROCKI C. M. , GLOVER T. D.
Published: December 2008

Spermatozoa in the ligatured cauda epididymidis of golden hamsters were tested for their fertilizing ability 12 days after hypophysectomy or after hypophysectomy and treatment with testosterone or human chorionic gonadotrophin (HCG). Fertility trials showed that the mean fertilization rate was reduced to approximately 65% of the control level, which contrasts sharply with the previously reported effects of castration, which led to the infertility of spermatozoa within 12 days as a result of androgen withdrawal.

The present study showed that loss of fertilizing ability in hypophysectomized animals was also due to a decrease in circulating androgens since treatment with testosterone or HCG (10 or 40 i.u./day) prevented the adverse effect of hypophysectomy. However, there was some indication that sperm survival might also be directly or indirectly dependent, in part, on hypophysial hormones. While daily doses of HCG (10 or 40 i.u./day) maintained fertilizing ability in hypophysectomized animals, treatment with intermediate doses (especially 20 i.u./day) reduced the mean fertilization rate to 40·8%. This paradoxical effect of HCG on sperm survival was shown not to be mediated by the adrenal glands: the magnitude of the effect was related to the amount of testicular tissue present. Thus, when only one testis was present the adverse effect of 20 i.u. HCG/day was reduced by approximately half whereas the spermatozoa retained a high fertilizing ability in animals that were both castrated and hypophysectomized and treated with testosterone. It is suggested that the biphasic effect of HCG is due to the peripheral conversion of limited but significant amounts of circulating testicular androgens into oestrogens which antagonize the effect of testosterone in the epididymis. Attention is drawn to the possibility that specific dose levels of HCG might also be detrimental to sperm survival in the treatment with gonadotrophins of infertility in men.
KINETIC STUDIES WITH 125I-LABELLED FOLLICLE-STIMULATING HORMONE
Authors: BUTT W. R. , RYLE MARGARET , SHIRLEY ANNE
Published: December 2008

Follicle-stimulating hormone (FSH) labelled with 125I which retained its biological activity was injected into immature mice. Accumulation in, and loss from, the ovaries and some other tissues were studied. The ovarian content was maximal 40 min after injection. By 30 min the specific radioactivity of the ovary was proportional to that of the blood. Previous injection of a large dose of unlabelled FSH reduced accumulation of 125I-labelled FSH by one-third only. Subsequent injection of a large dose of unlabelled FSH accelerated loss of 125I-labelled FSH. It was concluded (i) that the 125I-labelled FSH behaved like normal FSH; (ii) that the immature mouse ovary has numerous binding sites; (iii) that the attachment of FSH to the binding sites is labile; (iv) that the concentration in the ovary tends to equilibrate with that in the blood. Similar conclusions were drawn from parallel studies using cultured infantile mouse ovaries. These also suggested that depletion of 125I-labelled FSH from the ovary involved a second-order reaction.
THE SPECIFICITY OF AN OVINE PITUITARY INCUBATION SYSTEM LINKED WITH GONADOTROPHIN ASSAYS FOR DETECTING GONADOTROPHIN RELEASING ACTIVITY
Authors: HARTLEY BARBARA M. , CRIGHTON D. B. , LAMMING G. E.
Published: December 2008

A sheep pituitary incubation system was developed which may be used to study the release of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as assayed biologically. Specificity was examined by adding at high concentration various materials present in the hypothalamus, a crude acid extract of sheep cerebral cortex or crude or partly purified extracts of ovine hypothalamic tissue.

Of the materials tested for LH and FSH releasing activity, oxytocin, adrenaline, synthetic lysine vasopressin and cerebral cortex extract failed to influence LH or FSH release. Natural vasopressin containing unknown proportions of the lysine and arginine forms did not affect FSH release but produced a significant increase in the LH content of the medium, the reason for which was not clear. Noradrenaline failed to influence FSH release but produced an apparent depression in the LH content of the medium due to an action on the LH released or upon the ovarian ascorbic acid depletion assay since the addition of noradrenaline to standard ovine LH reduced the potency in the assay to an almost identical degree.

Extracts of ovine hypothalamic tissue consistently increased the LH and FSH content of the medium.

The method described may be applicable to the detection and estimation of LH and FSH releasing activity in ovine hypothalamic tissue extracts and to detecting changes in the responsiveness to hypothalamic stimulation of sheep pituitary tissue.
EFFECTS OF EXTENDED LACTATION AND 9α-FLUOROPREDNISOLONE ACETATE ON SERUM THYROXINE AND LACTATIONAL PERFORMANCE
Authors: LORSCHEIDER F. L. , MEARS G. J.
Published: December 2008

The effects of extending lactation up to 48 days on serum thyroxine (T4), and its relationship to lactational performance, were studied with rats fed a ration containing 1·0 μg I−/g of feed. The effects of chronic administration of 9α-fluoroprednisolone acetate on serum T4 during prolonged lactation were also determined. Lactation was prolonged by substitution of foster litters at 8-day intervals. Serum T4 was measured by a competitive protein-binding assay.

Chronic administration of 9α-fluoroprednisolone acetate up to 32 days resulted in a significant increase in serum thyroxine in non-lactating rats. In saline-treated rats lactating up to 48 days, serum T4 was initially reduced by 30% at 16 days, but progressively increased as lactational performance (expressed as gain in weight of pups) decreased. This inverse correlation was attributed to a progressive decline in mammary gland competition for iodine and to a progressive depletion of corticosterone which may have exerted an antithyroid effect initially. Rats treated with 9α-fluoroprednisolone acetate and lactating up to 48 days, had serum T4 levels which were lower than values for corresponding saline-treated lactating rats, but were similar to those levels observed in saline-treated non-lactating rats. This may indicate a higher rate of thyroid hormone utilization in lactating rats treated with 9α-fluoroprednisolone acetate and may also explain the ability of these rats to maintain a better lactational performance than saline-treated lactating rats. Comparisons of each 8-day extended lactation period showed that in all cases lactational performance was greater for mothers treated with 9α-fluoroprednisolone acetate; up to 113% more from 16 to 24 days lactation, up to 153% more from 24 to 32 days lactation, 146% more from 32 to 40 days lactation, and 317% more from 40 to 48 days lactation, despite the fact that by day 48 maternal body weight of lactating rats treated with 9α-fluoroprednisolone acetate was not different from that of saline-treated lactating rats. A hypothesis proposed for the hormonal maintenance of lactation suggests that the maintenance of euthyroid levels of serum T4 due to treatment with 9α-fluoroprednisolone acetate is necessary for the continued prolactin-induced mammary synthesis of fatty acids and nucleic acids. Both glucocorticoids and thyroxine may be rate limiting to milk synthesis.
CYTOCHROME P-450 ACTIVITY IN SHEEP CORPORA LUTEA DURING THE OESTROUS CYCLE
Authors: SIMPSON E. R. , JEFCOATE C. R. , COLLETT R. A. , LAND R. B.
Published: December 2008

Cytochrome P-450 of mitochondria from the ovine corpus luteum was examined on different days throughout the oestrous cycle. Most, if not all, of the mitochondrial cytochrome P-450 appeared to be of the type involved in cholesterol side-chain cleavage, as determined by steroid binding spectra. The content of mitochondrial cytochrome P-450 in the corpus luteum changed considerably throughout the cycle, and closely paralleled the rise and fall of plasma progesterone concentration; the correlation between these two parameters was 0·96. This was largely a reflection of the changes in weight of the corpus luteum throughout the cycle, since the specific content of cytochrome P-450 changed much less dramatically. The percentage of the mitochondrial cytochrome P-450 present as the cholesterol—substrate complex remained constant throughout the cycle at about 25–30% of the total.
STUDIES ON THE BINDING ACTIVITY FOR THE LONG-ACTING THYROID STIMULATOR
Authors: DIRMIKIS SUSAN , MUNRO D. S.
Published: December 2008

The binding activity of fresh human thyroid homogenates for the long-acting thyroid stimulator (LATS) was shown to be principally associated with the particulate fraction. LATS binding activity (LAA) could be partially released into the soluble fraction by freezing and thawing of thyroid homogenates. By delaying freezing and thawing until the particulate fraction had been washed repeatedly it was possible to obtain highly purified preparations of LAA.
EFFECT OF GONADOTROPHINS ON THE PRODUCTION OF STEROIDS BY SHEEP OVARIAN FOLLICLES CULTURED IN VITRO
Authors: MOOR R. M. , HAY MARY F. , McINTOSH J. E. A. , CALDWELL B. V.
Published: December 2008

The main objective of the study was to determine the rate at which Graafian follicles of sheep that had been treated with exogenous gonadotrophin acquire the ability to secrete oestrogen in vitro. Follicles were explanted from sheep 5 min to 24 h after injection of pregnant mare serum gonadotrophin (PMSG) and kept individually in culture for 7 days. The mean daily output of oestrogen by follicles from PMSG-treated sheep was higher than that secreted by follicles from untreated sheep. However, only a certain proportion of the follicles from each sheep secreted significant amounts of oestrogen in vitro; these follicles were called 'stimulated'. The proportion of stimulated follicles was 5% for control sheep, 20–30% for follicles explanted from sheep 5 min to 12 h after injection with PMSG, and 80% for follicles explanted from sheep that had been injected with PMSG 24 h previously.

In the second part of the study, the pattern of oestrogen and progesterone secretion by stimulated follicles of different sizes explanted from PMSG-treated sheep at various stages of the oestrous cycle was determined. Up to the 14th day, oestrogen production in vitro by follicles over 4·5 mm in diameter reached a maximum 2 days after PMSG injection and decreased thereafter; progesterone production rose steadily as the oestrogen levels declined. In contrast, follicles of less than 4·5 mm diameter secreted considerable amounts of oestrogen for the first 5 days in culture, but produced only small quantities of progesterone. In follicles explanted on day 15, oestrogen secretion decreased steadily from the beginning of the culture period and was very low by the 4th day. Most follicles explanted at oestrus secreted only small amounts of oestrogen in vitro but secreted large amounts of progesterone.