bluuebunny/crossref_metadata_2025_split huggingface dataset:
DYNAMICS OF PROGESTERONE METABOLISM IN THE PSEUDOPREGNANT RAT
Authors: ROBINSON J. , MERRY B. J. , LIGHTFOOT M. E. , HALL A. K. 
Published: December 2008

The characteristics of the disappearance of progesterone and 20α-dihydroprogesterone from blood were examined in rats made pseudopregnant by administration of gonadotrophins. Measurement of the disappearance of [3H]progesterone from blood indicated that progesterone metabolism can be represented by a two-compartment model in this animal preparation. The disappearance of [3H]progesterone from blood was described by two half-lives of 0·5 and 11·7 min. The metabolic clearance rate for this steroid was 2·9 litre/day, equivalent to a production rate of 3·9 μmol/day. The initial volume of distribution of the injected [3H]progesterone was 5·0 ml, a volume similar in size to the expected plasma volume. The total volume of distribution of [3H]progesterone (i.e. 'inner' and 'outer' pools) was in the range 24·8–35·4 ml.
The disappearance of endogenous progesterone from the blood of pseudopregnant rats after vascular isolation of the ovaries showed two half-lives of 1·1 and 11·4 min respectively. The disappearance of a product of reductive metabolism of progesterone, 20α-dihydroprogesterone, was apparently uniphasic, with a half-life of 41·3 min.
IMPORTANCE OF PERINATAL TESTOSTERONE IN SEXUAL DIFFERENTIATION IN THE MALE RAT
Authors: GOGAN F. , SLAMA A. , BIZZINI-KOUTZNETZOVA B. , DRAY F. , KORDON C. 
Published: December 2008

Testosterone secretion in the male rat was high during the late fetal and immediate postnatal periods. It then showed a rapid decrease 3 h after birth and remained low until puberty.
Male rats from mothers given daily injections of an antibody to testosterone during the week before delivery displayed an LH peak when they were adult, orchidectomized and implanted with oestradiol. However, the amplitude of the peak was far smaller than in female rats from the same mothers treated in the same manner.
Thus, the critical period during which testosterone triggers hypothalamic sexual differentiation is very close to birth, possibly starting at the end of the fetal period.
LONG-TERM EFFECTS OF LEUCINE AND ARGININE ON B-CELL FUNCTION OF CULTIVATED PANCREATIC RAT ISLETS
Authors: SCHÄFER G. , SCHATZ H. 
Published: December 2008

Leucine and arginine are well-known stimulators of insulin release, but they exert different actions on insulin biosynthesis in short-term incubations of isolated islets. In order to study their long-term effects on the B-cell, isolated rat islets were cultivated for 40 h in medium containing 0·5 or 3 mg glucose/ml supplemented with l-leucine (10 mmol/l) or l-arginine (10 mmol/l). After the culture the islets were incubated for 3 h with 2 mg glucose/ml without addition of the respective amino acid. Insulin biosynthesis was estimated from incorporation of [3H]phenylalanine or [3H]leucine into the (pro)insulin fraction of the islet proteins during this incubation.
At the low concentration of glucose, the leucine-cultivated islets released much more insulin than the control islets during culture as well as during subsequent incubation. At both glucose concentrations cultivation together with this amino acid resulted in an enhanced insulin biosynthesis.
The insulin-releasing effect of arginine with 0·5 mg glucose/ml was not as marked as that observed with an equimolar concentration of leucine. Islets cultivated with arginine showed no response to glucose during the incubation after culture. Hormone synthesis was found to be inhibited. Shortening of culture time to 20 h, followed by an additional 4 h of cultivation without arginine did not result in an improvement of B-cell function after culture.
It is concluded that leucine, in contrast with arginine, supports B-cell function, especially insulin biosynthesis, during long-term culture of islets. Stimulation of release of insulin with a concomitant inhibition of insulin biosynthesis caused by arginine during culture did not lead to a compensatory increase in hormone synthesis after culture.
EFFECTS OF TRIMETHOPRIM AND SULPHONAMIDE PREPARATIONS ON THE PITUITARY–THYROID AXIS OF RODENTS
Authors: COHEN H. N. , FYFFE J. A. , RATCLIFFE W. A. , McNICOL A. M. , McINTYRE H. , KENNEDY J. S. , THOMSON J. A. 
Published: December 2008

The effects on pituitary–thyroid function of the commonly prescribed anti-bacterial preparations co-trimoxazole and co-trifamole, and their component drugs, have been studied in the rat and compared to the changes caused by propylthiouracil.
Co-trimoxazole and co-trifamole, in doses 20-fold in excess of a pharmacological dose administered for 10 days, produced marked changes in hormone levels consistent with blocking of thyroidal activity. Significant increases in thyroid gland weight, with histological evidence of hyperplastic goitre formation, were also demonstrated. Propylthiouracil produced less marked changes of thyroid hormone levels but higher levels of thyroid-stimulating hormone. Pharmacological doses of co-trimoxazole and co-trifamole and sulphamoxole, the sulphonamide component of co-trifamole, caused significant changes in thyroid hormone levels consistent with anti-thyroidal activity. In contrast, there was no evidence that trimethoprim, which is common to both preparations, or sulphamethoxazole, the sulphonamide component of co-trimoxazole, had an anti-thyroidal action, indeed, serum thyroxine levels were significantly increased at pharmacological dosage. We have concluded that the new commonly prescribed combination preparations retain the goitrogenic properties of the earlier sulphonamides.
AGE- AND MENTAL HEALTH-RELATED CIRCADIAN RHYTHMS OF PLASMA LEVELS OF MELATONIN, PROLACTIN, LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE IN MAN
Authors: TOUITOU YVAN , FÈVRE MICHÈLE , LAGOGUEY MICHEL , CARAYON ALAIN , BOGDAN ANDRÉ , REINBERG ALAIN , BECK HERVÉ , CESSELIN FRANÇOIS , TOUITOU CATHERINE 
Published: December 2008

Circadian changes in plasma levels of melatonin, prolactin, LH and FSH were studied in four groups: seven healthy young men, six elderly men, six elderly women and six elderly demented patients (two men and four women). The daily activities of the subjects were synchronous and blood samples were taken every 4 h.
The 24-h mean concentrations of prolactin in plasma were the same in all groups, whereas those of LH and FSH were twice as high in the elderly as in the young men and eight and 23 times higher respectively in the elderly women. The 24-h mean plasma levels of melatonin in the elderly were half those in the young, but were not influenced by the sex or mental condition of the subjects.
A statistically significant circadian rhythm for melatonin was defined in the four groups, for prolactin in all groups except the elderly men and for LH only in the demented patients and in the young men. No circadian rhythm could be detected for FSH in any of the four groups. The acrophases of melatonin and prolactin ranged between 02.30 and 04.00 h, those of LH (when a rhythm was validated) clustered around 01.00 h.
The circadian rhythms of plasma levels of melatonin, prolactin and LH are not modified in old age nor in dementia. A positive correlation has been demonstrated in young men between melatonin and LH and between melatonin and prolactin, but no such correlation could be found in the elderly.
INSULIN RELEASE FROM THE PERFUSED RAT PANCREAS, STIMULATED BY PERIFUSATES OF THE PITUITARY NEUROINTERMEDIATE LOBES OF GENETICALLY OBESE AND LEAN MICE
Authors: DUNMORE SIMON , BELOFF-CHAIN ANNE 
Published: December 2008

The perfused rat pancreas has been used to study the dynamics of insulin release during stimulation with a perifusate of the pituitary neurointermediate lobe (NIP) of genetically obese mice (ob/ob) and their lean litter-mates (+/+). It has been shown that the NIP of ob/ob mice is more active. The remainder of the study was carried out with NIP from ob/ob mice. The results showed that both phases of insulin release stimulated by 16·6 mm-glucose were increased by NIP. When the pancreas was first stimulated with NIP in the presence of 5·5 mm-glucose, followed by a high concentration of glucose, it responded to the latter with a normal biphasic response. If, however, the pancreas was stimulated first with glucose the response to NIP was refractory.
The results are discussed in relation to the possible significance of an insulin secretagogue from the pituitary pars intermedia in the hyperinsulinaemia associated with obesity.
NORMAL FUNCTION OF EXTRA-ADRENAL CHROMAFFIN TISSUES IN THE YOUNG RABBIT AND GUINEA-PIG
Authors: COUPLAND R. E. , KENT CHRISTINE , KENT S. E. 
Published: December 2008

An attempt has been made to determine the relative functional activities of adrenal and extra-adrenal chromaffin tissue during the neonatal phase and up to 1 week of age using young rabbits and guinea-pigs whose main extra-adrenal abdominal para-aortic chromaffin bodies are respectively non-innervated and innervated.
Amine synthesis and storage were followed by assay and autoradiography after a single intraperitoneal injection of l-[2,5,6-3H]DOPA and the findings correlated with amine content as assessed by high performance liquid chromatography and by volume of tissue.
The results indicate that in the guinea-pig, in spite of differences in proportions of adrenaline and noradrenaline in the adrenal gland and para-aortic body (PAB), the loss of labelled catecholamines from the innervated PAB closely follows that from the adrenal medulla, suggesting that both participate in normal sympathoadrenal activity. By comparison, in the rabbit the PAB shows only a minimal decrease in labelled amine during the first week of life during which period the amine content and concentration of the PAB doubles: the functional significance of this non-innervated extra-adrenal chromaffin tissue, which persists throughout life, has still to be determined.
Androgen and oestrogen concentrations in the ovary of the cyclic rat
Authors: Toorop A. I. , Gribling-Hegge L. 
Published: December 2008

In the 5-day cyclic rat the ovarian androgen and oestrogen concentrations, measured by radioimmunoassay, started a gradual rise on the day of metoestrus, reaching maximal values in the period from 22.00 h on dioestrus 2 until 17.00 h on the day of pro-oestrus. A steep decline in the ovarian androgen and oestrogen concentrations occurred between 17.00 and 21.00 h on the day of pro-oestrus.
Rats, injected intraperitoneally with an ovulation-blocking dose of pentobarbitone sodium (35 mg/kg body weight) at 13.00 h on the day of pro-oestrus, tended to show a decline in ovarian concentrations of androgens and oestrogens during late pro-oestrus, but this decrease was less steep than in saline-injected rats. At 10.00 and 14.00 h on the day after pro-oestrus the ovarian concentrations of androgens and oestrogens in rats treated with pentobarbitone sodium showed a further decline but values were still higher than those in saline-treated oestrous rats. At 17.00 h, i.e. 28 h after injection with pentobarbitone sodium, a distinct increase in the ovarian androgen and oestrogen concentrations was noted and a steep decline was observed at 21.00 h on the day after pro-oestrus.
Thus normal as well as delayed ovulation was preceded first by an increase and then by a steep decline in ovarian concentrations of oestrogens and androgens.
Distribution of 125I-labelled follicle-stimulating hormone and human chorionic gonadotrophin in the gonads of hypogonadal (hpg) mice
Authors: Charlton H. M. , Parry Dilys , Halpin D. M. G. , Webb R. 
Published: December 2008

Hypogonadal mice are deficient in LH releasing hormone (LH-RH), the releasing factor for LH and FSH, with a consequent failure of postnatal ovarian and testicular development. After intravenous injection of hypogonadal females with 125I-labelled human chorionic gonadotrophin (hCG), followed by autoradiography of semi-thin (1 μm) slices of the ovary, labelled hCG was found to be associated with interstitial cells and thecal cells with little or no labelling of granulosa cells. Labelled human FSH was associated solely with granulosa cells. Hypogonadal females, implanted for 5 days with a silicone elastomer capsule of oestrogen, showed a similar response to that of normal females with hCG labelling of the granulosa cells of the larger follicles as well as of the thecal cell layer. Furthermore, subcutaneous injection of hypogonadal females with LH-RH (50 ng), 12 times daily for 5 days, increased uterine weight and stimulated ovarian development with some large follicles binding hCG to both thecal and granulosa cells. Therefore stimulation of follicular development may possibly be associated with increased oestradiol concentrations.
In the male, after injection of 125I-labelled hCG, silver grains were associated with the interstitial cells alone in both hypogonadal and normal mice. Labelled human FSH was undetectable in semi-thin testicular sections, but the mode of injection (intravenous) may not have allowed enough labelled hormone to reach the testis in order to resolve the question as to whether the hypogonadal or normal testis can bind FSH.
In-vivo uptake and metabolism of testosterone by the skin and other tissues of the rat
Authors: Randall Valerie A. , Ebling F. J. , Hargreaves G. 
Published: December 2008

The uptake and metabolism of radioactively labelled testosterone was investigated in vivo at various time intervals in the skin, plasma and other tissues of adult rats castrated 24 h earlier. After the addition of marker steroids the components of the tissue extracts were separated by partition and development in several chromatographic systems; steroid identification was confirmed by derivative formation and recrystallization to constant 3H:14C ratio.
The skin resembled the classical androgen target organs in the uptake and retention of both total and unconjugated radioactivity, but the actual composition of the radioactivity present in the skin was markedly different from that in the accessory glands. Little testosterone was recovered from the ventral prostates and 5α-dihydrotestosterone (5α-DHT), often considered the active intracellular androgenic steroid, constantly occupied the largest proportion of the extracted radioactivity. In the skin samples, however, testosterone was always the major unconjugated steroid detected and 4-androstene-3,17-dione, 5α-DHT, 5α-androstane-3α,17β-diol, androsterone and 5α-androstane-3β,17β-diol were only identified in much smaller quantities, even after 5 h. Although the majority of the plasma radioactivity was conjugated or very polar by 20 min, all the steroids found in the skin were present, albeit in different proportions; testosterone was always predominant and 5α-androstane-3β,17β-diol was also detected in larger amounts than the very low levels of the other steroids.
The results suggest that 5α-DHT is not as important in the skin as it is in the prostate of the rat and that other androgenic steroids, most notably testosterone itself, may be involved in the mechanism of androgen action in the skin.
An assay of the capacity of biological fluids to stimulate renal glucose-6-phosphate dehydrogenase activity in vitro as a marker of their ability to inhibit sodium potassium-dependent adenosine triphosphatase activity
Authors: Fenton S. , Clarkson E. , MacGregor G. , Alaghband-Zadeh J. , de Wardener H. E. 
Published: December 2008

A highly sensitive cytochemical method for the assay of the ability of plasma and extracts of human urine to stimulate renal glucose-6-phosphate dehydrogenase (G6PD) activity in vitro is described. In the proximal convoluted tubules there was a linear increase of G6PD activity with the logarithm of concentration of a highly purified natriuretic extract from normal human urine (0·384–384 ng active material/l) which was used as a standard. The stimulation of G6PD obtained with dilutions of normal human plasma was parallel to that produced by the standard. The sensitivity of the assay permitted the measurement of as little as 0·384 ng active material/l of the natriuretic extract (0·001 units/ml) and dilutions of 1/10 000 could be detected using normal human plasma. The mean ± s.e.m. index of precision was 0·068± 0·003 (n = 9).
It is known that inhibition of sodium potassium-dependent adenosine triphosphatase (Na+-K+-ATPase) is associated with a rise in G6PD activity. We have confirmed this observation by demonstrating that ouabain, a potent inhibitor of Na+ -K+-ATPase, stimulates renal G6PD activity in our assay and that natriuretic extract, human plasma and ouabain stimulated renal G6PD activity in vitro and simultaneously inhibited renal Na+-K+-ATPase activity in vitro.
The plasma from 12 normal subjects (five of whom were previously shown to inhibit renal Na+-K+-ATPase activity in vitro in a manner related to sodium intake) stimulated renal G6PD activity in vitro, and this activity was also directly related to sodium intake.
It is suggested that the change in the capacity of plasma to stimulate renal G6PD activity in vitro is a marker of the concentration of a circulating sodium transport inhibitor.
Effect of composition of incubation medium on aldosterone and corticosterone production by isolated rat zona glomerulosa cells
Authors: Campbell D. J. 
Published: December 2008

The role of the composition of the incubation medium in determining the steroidogenic responsiveness of collagenase-dispersed rat zona glomerulosa cells was examined by studying the effect on production of aldosterone and corticosterone of (1) changes in the bovine serum albumin (BSA) concentration in Krebs–Ringer bicarbonate buffer (KRBGA), (2) dialysis of the BSA and (3) comparison of KRBGA with 'modified' Medium 199. Medium 199 was modified so that its electrolytic content was identical to that of KRBGA.
Compared with 0·1–0·2% BSA in KRBGA, BSA concentrations of 0·5 and 4% caused inhibition of both basal and K+-stimulated, but not angiotensin II-stimulated steroidogenesis. This inhibitory property of BSA was not removed by dialysis. The BSA did, however, contain a dialysable factor which increased both basal steroidogenesis and the steroidogenic response to maximal K+ and angiotensin II stimulation.
Both incubation media contained 0·2% BSA for the comparison of KRBGA with modified Medium 199. Modified Medium 199 increased both basal steroidogenesis and the aldosterone response to K+ stimulation (per cent increase above basal) by two- to threefold compared with KRBGA, with smaller increases in the response to ACTH and 5-hydroxytryptamine (5-HT) and a decrease in the response to cyclic AMP. In contrast, modified Medium 199 increased the aldosterone response to angiotensin II by sevenfold, from 60% (in KRBGA) to 420%.
In KRBGA, angiotensin II inhibited K+-stimulated aldosterone production. This effect was produced by concentrations of angiotensin II below the threshold for steroidogenesis and could be reproduced with the angiotensin II antagonist [Sar1, Ileu8]-angiotensin II. Angiotensin II did not inhibit K+-stimulated aldosterone production in modified Medium 199.
These data emphasize the importance of the composition of the incubation medium in determining the steroidogenic responsiveness of rat zona glomerulosa cells in vitro. Furthermore, these data indicate that the steroidogenic response to angiotensin II, compared with K+, ACTH, 5-HT and cyclic AMP, is more readily influenced by other, as yet unidentified, factors in the incubation medium, and are consistent with recent evidence that angiotensin II and K+ do not share a common mode of action on steroidogenesis by these cells.
Inter-species comparison of somatomedin structure using immunological probes
Authors: Wilson D. M. , Hintz R. L. 
Published: December 2008

To explore the structural differences in various animal somatomedins, we examined the sera of 20 animal species using two region-specific radioimmunoassays, a radioimmunoassay specific for somatomedin-C and a placental membrane radioreceptor assay. Using small peptide portions of the insulin-like growth factor-I (IGF-I) C chain and D chain made by solid-state methods, we generated antisera in rabbits and developed radioimmunoassays to these regions. For a radioimmunoassay directed against intact somatomedin-C, we used the antibody distributed by the NIH (NIH-radioimmunoassay). For the detection of somatomedin peptide content, we used a placental membrane radioreceptor assay. 125I-Labelled IGF-I was used as the radioligand in all assays and an insulin-free, partially purified somatomedin preparation was used for the standard curves. All samples were chromatographed in 0·25 m-formic acid to remove any somatomedin-binding protein before assay.
The correlation between the radioreceptor assay and the NIH-radioimmunoassay was good (r2 = 0·84) but the slope was significantly (P<0·001) different from a value of 1 which would be expected if the two assays were detecting equal amounts of somatomedin activity. In all the species, the somatomedin level measured by radioreceptor assay was greater than that measured by the NIH-radioimmunoassay, suggesting the presence of a somatomedin-like protein which has retained its ability to bind to the somatomedin receptor but which is sufficiently different to give it reduced affinity in the NIH-radioimmunoassay.
The somatomedins of rat, hamster and mouse (all rodents of the superfamily Myomorpha) were not detectable using the radioimmunoassays for the C and D chains of IGF-I, although they were high in the radioreceptor assay. This suggests that these regions have a different structure from the analogous regions in the guinea-pig (a rodent of the superfamily Caviomorpha) and implies a significant structural change in a somatomedin-like molecule during the evolution of the order Rodentia. This is analogous to the marked differences in the known sequence of the pro-insulins in these two superfamilies.
The International Reference Preparation of Gonadorelin for Bioassay: a comparison with different preparations of synthetic luteinizing hormone releasing hormone using physicochemical methods of analysis, different bioassays and immunoassay
Authors: Storring P. L. , Corran P. H. , Gaines Das Rose E. , Calam D. H. 
Published: December 2008

The preparation and nature of the International Reference Preparation of Gonadorelin for Bioassay (IRP; coded 77/596) are described.
The IRP was studied by four laboratories in four countries and compared, using physicochemical methods of analysis, various bioassay procedures and immunoassay, with preparations of synthetic luteinizing hormone releasing hormone (LH-RH) produced by different manufacturers.
Analyses by thin-layer chromatography and by reverse-phase high-performance liquid chromatography (HPLC) indicated some heterogeneity of the peptide present in most of these preparations of synthetic LH-RH, including that of the IRP; the latter preparation appeared to be 88·3% (w/w) pure, judged by HPLC. The data from the collaborative study suggested that each ampoule of the IRP contains approximately 31 nmol LH-RH.
The IRP appeared to be suitable to serve as an international reference preparation for bioassay since its behaviour was similar in different bioassays, so far as this could be examined, to that of the other preparations of LH-RH with which it was compared. Furthermore, the biological activities of different preparations of LH-RH, assessed in terms of the IRP, appeared to correlate with their degrees of purity assessed by physicochemical methods, suggesting that the peptides other than LH-RH present in the IRP did not contribute significantly to the biological activity of the preparation in these assay procedures. The limited data available suggested that the IRP might also be suitable as a reference preparation for immunoassay.
The ampouled preparation, coded 77/596, was therefore established by the World Health Organization as the International Reference Preparation of Gonadorelin for Bioassay and assigned a unitage of 31 i.u./ampoule on the basis that the i.u. is represented by 1 nmole of LH-RH.