bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF 2-BROMO-α-ERGOCRYPTINE (CB154) ADMINISTRATION ON THE HORMONE LEVELS, ORGAN WEIGHTS, PROSTATIC MORPHOLOGY AND ZINC CONCENTRATIONS IN THE MALE RAT
Authors: Harper M. E. , Danutra V. , Chandler J. A. , Griffiths K.
Published: December 2008

2-Bromo-α-ergocryptine (CB154) administration to male rats produced a significant decrease in plasma prolactin levels without changing the LH and testosterone concentrations. The weights of the accessory sex tissues, testes, adrenals and kidney were unaltered by the treatment. Zinc concentration and distribution in the cell organelles of the prostatic tissue was markedly changed by CB154 treatment. No changes in the uptake of testosterone in vivo occurred in the treated animals. Prolactin did not consistently influence the prostatic adenyl cyclase activity in vitro and only at high concentrations was the testosterone uptake in vitro with cultures of prostatic tissue increased.
THE SERUM HALF-LIFE OF SOMATOMEDIN ACTIVITY: EVIDENCE FOR GROWTH HORMONE DEPENDENCE
Authors: Cohen Kenneth L. , Nissley S. Peter
Published: December 2008

The serum half-life of somatomedin (SM) activity has been measured following the intravenous injection of SM activity into hypophysectomized rats. A [3H]thymidine incorporation assay in chick embryo fibroblasts (CEFs) has been utilized to measure SM activity. Cell cycle analysis data obtained with the flow microfluorometer shows that the [3H]thymidine incorporation data reflects actual DNA synthesis. When normal rat serum was injected, a half-life for SM activity of approximately 3 h was determined. In marked contrast, when serum from hypophysectomized (hypox) rats acutely treated with growth hormone (GH) was used as the source of SM actively, the half-life of the SM actively was short, approximately 8 min. However, when serum from hypox rats chronically treated with GH was injected, the half-life was again long, approximately 4 h. SM activity has been separated from its binding proteins by boiling under acid conditions or chromatography on Sephadex G-50 in 1 n acetic acid. The halflife of this partially purified SM activity was short, in the range of 10–30 min. Finally, recombination of the partially purified SM activity with the large proteins in normal serum extended the half-life of the SM from 10–30 min to about 2 h. These data indicate that the serum half-life of SM activity is GH dependent and suggest that the serum binding protein, like SM itself, is under GH control.
MEDULLARY THYROID CARCINOMA: ECTOPIC PRODUCTION OF PEPTIDES WITH ACTH-LIKE, CORTICOTROPHIN RELEASING FACTOR-LIKE AND PROLACTIN PRODUCTION-STIMULATING ACTIVITIES
Authors: Birkenhäger Jan C. , Upton G. Virginia , Seldenrath H. Jaqueline , Krieger Dorothy T. , Tashjian Armen H.
Published: December 2008

A 45-year-old women had medullary thyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone.

A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.
FACTORS INFLUENCING TRIIODOTHYRONINE BINDING PROPERTIES OF LIVER NUCLEAR RECEPTORS
Authors: Degroot Leslie J. , Torresani Janine , Carrayon Pierre , Tirard Alain
Published: December 2008

Triiodothyronine (T3) may bind directly to receptors present in liver cell nuclei, or may be transported into nuclei by receptor protein(s) present in the cytosol. To evaluate these possibilities, T3 binding was studied in vitro using liver cell nuclei isolated from rats exposed in vivo to very low (H), normal (N), or high levels of T3 (H + T3), and using nuclei incubated in vitro with added cytosol proteins. Ka for T3 was 0.075 ± 0.05 × 1010 m−1 in N, 0.1+0.04 in H, and 0.094 + 0.04 in H + T3, and pg T3 bound/100 μg DNA were 47 ± 17, 31 ± 14, and 29 ± 8 in the three groups. The data indicate no difference in binding capacity between the groups related to prior in vivo exposure to T3, and that T3 may bind directly to empty nuclear receptor sites.

Rat liver cytosol proteins added to the in vitro incubation medium always depressed T3 uptake by nuclei. Bovine serum albumin had a similar effect. Large amounts of rat serum proteins depressed uptake, but low levels augmented T3 binding through an unknown mechanism.

It is probable that free T3 in serum is in equilibrium with free T3 in the cytosol and nucleus, and binds directly to nuclear receptor proteins without mediation by a cytosol receptor protein.
THE UPTAKE IN THE PANCREATIC ISLETS OF NICOTINAMIDE, NICOTINIC ACID AND TRYPTOPHAN AND THEIR ABILITY TO PREVENT STREPTOZOTOCIN DIABETES IN MICE
Authors: Tjälve Hans , Wilander Erik
Published: December 2008

The uptake of the nicotinamide adenine dinucleotide (NAD)-precursors nicotinamide, nicotinic acid and tryptophan in the pancreatic islets of mice was studied by use of autoradiographical methods. The ability of these substances to prevent streptozotocin diabetes was studied in the same species. It was found that only nicotinamide was strongly accumulated in the pancreatic islets and nicotinamide was also the only NAD-precursor which protected against the streptozotocin diabetes. Apparently there is a relationship between the ability of the NAD-precursors to be taken up in the pancreatic islets and their ability to prevent streptozotocin diabetes.
PRELIMINARY OBSERVATIONS OF BOVINE ADRENAL FASCICULATA-RETICULARIS CELLS IN MONOLAYER CULTURE: STEROIDOGENESIS, EFFECT OF ACTH AND CYCLIC AMP
Authors: Goodyer Cynthia G. , Torday John S. , Smith Barry T. , Giroud C. J. P.
Published: December 2008

Bovine adrenocortical cells dispersed by trypsin digestion of fasciculata-reticularis minces were maintained in monolayer culture for up to 6 weeks.

During the first week cells grown in medium containing ACTH (1 mU/ml) secreted steroids at a rate 10 to 20-fold greater than control cultures, cortisol accounting for 80–90% of the corticotrophic response. Using tracer amounts of [3H]progesterone and [3H]pregnenolone, the major products were cortisol, corticosterone, 11-deoxycortisol and 11-deoxycorticosterone in decreasing order of magnitude.

After 10 to 15 days in culture steroidogenesis was no longer enhanced by ACTH. This was concomitant with an apparent loss of 11β-hydroxylase activity which was mainly manifested by a sharp increase in the formation of 11-deoxycortisol.

Short-term incubations of these cells during the first week in culture provided evidence that steroidogenesis was related to ACTH concentrations (from 0.1 to 100 μU/ml) and stimulated by dibutyryl cyclic AMP, the corticotrophic responses being further enhanced by theophylline (0.5 to 50 μmoles/5 ml). Exposure of the cells to ACTH (50 μU/ml) resulted in a rapid increase in intracellular cyclic AMP concentrations concomitant with a progressive increase in the corticosteroids released into the medium.

The data are consistent with the conclusion that during the first week in culture these cells provide a valuable model for the study of factors regulating steroidogenesis in the zona fasciculata-reticularis.
OESTROGEN IN HUMAN PREGNANCY FAECES
Authors: Adlercreutz Herman , Martin Finian
Published: December 2008

The oestrogen content of two 24 h pools of pregnancy faeces, obtained from 2 normal women in the 33rd–37th week og gestation, was studied. The qualitative analyses were made by gas chromatography - mass spectrometry and the quantitative analyses by mass fragmentography. The presence of the following oestrogens in pregnancy faeces was established: Oestriol, oestrone, oestradiol-17β, 16-epioestriol, 17-epioestriol, 16α-hydroxyoestrone, 16-oxo-oestradiol-17β, 15α-hydroxyoestrone and 15α-hydroxyoestradiol-17β. In addition, mass fragmentographic evidence was obtained for the presence of 16β-hydroxyoestrone, 2-methoxyoestrone and oestradiol-17α. The total oestrogen excretion determined in the two pools was 786 and 1300 μg per 24 h. Unconjugated oestrogens accounted for 97.8 and 98.6% of these amounts, respectively.

Oestriol, oestradiol-17β, 15α-hydroxyoestradiol-17β, 16-epioestriol and oestrone, in that order, were quantitatively the most significant of the oestrogens determined. The remarkably high levels of oestradiol-17β found in faeces show, that in pregnancy, this mode of excretion is as important as urine for the elimination of this biologically active steroid. It is suggested that some of the oestradiol may have been formed through bacterial enzyme action from other oestrogens or neutral steroids.

Only trace amounts of ring D α-ketolic oestrogens were found in faeces. This is in marked contrast to the considerable amounts of these steroids found in pregnancy bile and urine.
EFFECTS OF SEX STEROIDS ON SEROTONIN UPTAKE IN BLOOD PLATELETS
Authors: Ehrenkranz Joel R. L.
Published: December 2008

Blood platelets have been suggested as a model for serotonin uptake and storage in the brain. To examine possible effects of sex steroids, platelets from human volunteers were incubated for 15 min with oestradiol, testosterone, and dihydrotestosterone, and then incubated for 1 min with radioactive serotonin. The effects of the various steroids on serotonin uptake were measured.

At 10−3 m, oestradiol decreased serotonin uptake by 70 %, testosterone by 49 %, and dihydrotestosterone by 25 %. Both oestradiol and testosterone showed maximal enhancement of uptake at 10−6 m; oestradiol increased serotonin uptake by 41 %, and testosterone by 60 %. Dihydrotestosterone maximally facilitated uptake by 40 % at a concentration of 10−4 m.

No sex differences were found in either direction or in magnitude of change in uptake due to any hormone. It is suggested that the effects of oestradiol are of physiological significance and that the site of action of the steroid effect on serotonin uptake is the cell membrane of the platelets.
BIOLOGICAL EFFECTS OF A NEW AND POTENT PROGESTAGEN. A CLINICAL STUDY
Authors: Viinikka Lasse , Ylikorkala Olavi , Nummi Simo , Virkkunen Pekka , Ranta Tapio , Alapiessa Unto , Vihko Reijo
Published: December 2008

The biological effects of a new synthetic progestagen, Org 2969 (13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17-ol) were studied in healthy normally menstruating women. Two of them were given 0.125 mg, five 0.060 mg and two 0.030 mg of Org 2969 daily on days 1–20 during one menstrual cycle. Serum levels of follicle stimulating hormone, luteinizing hormone, progesterone and oestradiol were analyzed on days 8–23 in order to evaluate the function of the hypophyseal-ovarian axis. The serum concentrations of aspartate amino transferase, alanine amino transferase, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin were determined to evaluate possible side effects on liver function on days 8, 15 and 23. Serum cortisol was measured on days 8 and 23. The basal body temperature was recorded daily during the whole cycle, and endometrium biopsies were taken on days 21 or 22 of the cycle. All samples were taken similarly during the treatment cycle and the preceding control cycle. According to the hormone determinations, all the treatment cycles were anovulatory except in one woman receiving the lowest dose. The treatment led to decreased spinnbarkeit, arborization and sperm penetration in the cervical mucus. Liver function tests and serum cortisol remained unchanged during the treatment.
OLIGOMERIC OESTRADIOL ESTERS: A NEW CLASS OF LONG-ACTING OESTROGENS
Authors: Kuhl Herbert , Auerhammer Walter , Taubert Hans-Dieter
Published: December 2008

Dimeric and trimeric oestradiol derivatives were administered as single subcutaneous injections into ovariectomized rats and the duration of oestrogenic effect was determined by means of daily vaginal smears. It could be shown that these preparations have a very protracted oestrogenic effect, and their threshold dose is considerably higher as compared to monomeric oestradiol diacetate. A dimeric compound containing one free hydroxy group caused a relatively even response in all animals with a linear relationship between the logarithm of dose and the duration of action. The effect was even more protracted when fully esterified dimeric or trimeric oestradiol succinates were used, but occurred in a more scattering manner. The duration of effect of 40 μg of the trimeric compound exceeded that of the equivalent dose of oestradiol undecylate. It is conceivable that the depot-effect of these oestradiol derivatives is due to delayed elimination.
ANALYSIS OF SUCKLING-INDUCED CHANGES IN ADENOHYPOPHYSEAL PROLACTIN CONCENTRATION IN THE LACTATING RAT BY THREE ASSAY METHODS
Authors: Nicoll C. S. , Mena F. , Nichols C. W. , Green Suzanne H. , Tai Mary , Russell Sharon M.
Published: December 2008

Suckling-induced changes in adenohypophyseal prolactin (PRL) concentrations in lactating rats were measured in two experiments by three assays: a disc electrophoretic assay (DEA), a bioassay (BA) and a radioimmunoassay (RIA). Substantial discrepancies among the three assays were found in the absolute amounts of pituitary PRL measured and in the changes in adenohypophyseal PRL concentration that were recorded between suckling intervals. The results indicate that in dynamic states of secretory activity the correspondence among BA, RIA and DEA estimates of pituitary PRL concentration is poor.
HORMONAL AND BIOCHEMICAL CHANGES IN PATIENTS SUCCESSFULLY OPERATED FOR PRIMARY HYPERPARATHYROIDISM
Authors: Muls E. , Bouillon R. , De Moor P.
Published: December 2008

Six patients with primary hyperparathyroidism were studied during the first seven days after the operative removal of the parathyroid adenoma with special emphasis on biochemical and hormonal changes during the first 24 h. Serum parathyroid hormone (PTH) levels fell abruptly after the parathyroidectomy and normalized within 3 h. The half-life of the biologically inert c-terminal PTH-fragment (M. W. 7000–7500) was calculated to be about 180 min. No significant changes in serum calcitonin levels were found. The serum phosphorus levels, which were already low pre-operatively, decreased transiently but significantly during the first 90 min after the removal of the parathyroid adenoma. This fall in serum phosphorus preceded a slow decrease of the calcaemia. During the first post-operative week the calcaemia continued to decline, while serum phosphorus levels increased. The pre-operative cholesterol levels were low compared to age-paired normal Belgians. During the first post-operative week the cholesterolaemia decreased even more, whereas at long term follow-up a clearcut increase of the serum cholesterol levels has to be expected.
A STUDY OF INSULIN RECEPTORS IN HUMAN MONONUCLEAR LEUCOCYTES
Authors: Pedersen Oluf , Beck-Nielsen Henning
Published: December 2008

Insulin binding sites were demonstrated in human mononuclear leucocytes by use of a technique which includes isolation of mononuclear leucocytes from defibrinated blood and separation of cell bound and free [125I] insulin with silicone oil.

The binding was time and temperature dependent. At 15°C equilibrium was reached after 90 min and a plateau maintained for at least 50 min. Incubations were carried out at 4°C, 15°C and 37°C. Maximal binding was obtained at 15°C. The optimum pH for insulin receptor interaction occurred at about 8. [125I] insulin binding to mononuclear leucocytes was demonstrated to be a linear function of cell number concentration over a range of 17–70× 106×ml−1. The binding was a displaceable function of native insulin concentration.

In a group of 21 young healthy persons with normal body weight we found a mean specific cell binding fraction of 1.92 ± 0.58 (s) × 10−2. Analysis of the equilibrium between insulin and its receptor revealed an apparent heterogeneity of insulin receptors.
METABOLISM OF 20β-HYDROXY-4-PREGNEN-3-ONE IN UTERINE TISSUE OF NON-PREGNANT RATS IN VITRO
Authors: Lisboa B. P. , Holtermann M.
Published: December 2008

In vitro experiments carried out with uterus preparations of ovariectomized adult rats indicate the presence in this tissue of a 20β-hydroxysteroid-oxidoreductase which catalyzes the conversion of 20β-hydroxy-4-pregnen-3-one to progesterone.

Since a hepatic 20β-hydroxysteroid-oxidoreductase is absent in adult female rats, the myometrial enzyme can be responsible for the biological activity of 20β-hydroxy-4-pregnen-3-one in these animals.

Besides progesterone five metabolites were isolated and identified after incubation of [4-14C]20β-hydroxy-4-pregnen-3-one with uterine tissue: 20β-hydroxy-5α-pregnan-3-one, 20β-hydroxy-5β-pregnan-3-one, 5α-pregnane-3α,20β-diol, 4-pregnene-3α,20β-diol and 4-pregnene-3β,20β-diol. The conversion of 20β-hydroxy-4-pregnen-3-one to progesterone permits us to regard all five steroids isolated as progesterone metabolites in the rat uterus.

20β-hydroxy-5β-pregnan-3-one is the first C21-metabolite with a 5β(H)-configuration isolated in the rat uterus, which indicates the presence of 5β-reductase in this tissue.
PROGESTERONE-INDUCED AUGMENTATION OF PITUITARY GONADOTROPHIN RESPONSES TO LUTEINIZING HORMONE-RELEASING HORMONE IN OESTROGEN-PRE-TREATED AMENORRHOEIC WOMEN
Authors: Nillius Sven Johan , Wide Leif
Published: December 2008

Modulating effects of oestradiol-17β and progesterone on the pituitary responsiveness to luteinizing hormone-releasing hormone (LRH) were investigated in 12 women with functional amenorrhoea. The pituitary reserve capacity for gonadotrophin section was investigated with repeated intravenous LRH tests before and after administration of oestradiol-1β followed by either progesterone or saline. Intramuscular injection of 1 mg of oestradiol-17β benzoate resulted in a suppression of both the basal gonadotrophin levels in serum and the gonadotrophin responses to LRH 24 h later. Progesterone, 25 mg im, was then administered in eleven experiments. Six h later, when the mean serum progesterone level had increased to levels similar to those seen in the early post-ovulatory phase of the menstrual cycle, there was a marked augmentation of the pituitary capacity to release both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in response to LRH. This was not found in eight experiments where saline was given instead of progesterone after oestrogen pretreatment. These findings suggest that the greatly increased pituitary sensitivity to LRH at midcycle may be caused not only by the oestradiol increase in blood during the late follicular phase but also in part by the small pre-ovulatory rise of progesterone during the mid-cyclic LH peak. Furthermore, they add further support to the hypothesis that progesterone as well as oestradiol is involved in the induction of the LH peak at midcycle. Progesterone may be of importance to secure the release of enough LH for ovulation and normal corpus luteum formation to occur.
PROLACTIN IN THE RAM: SEASONAL VARIATIONS IN THE CONCENTRATION OF BLOOD PLASMA FROM BIRTH UNTIL THREE YEARS OLD
Authors: Ravault J. P.
Published: December 2008

Peripheral prolactin levels were measured by radioimmunoassay in nine Ile de France rams, born in autumn and reared under natural conditions of light and temperature until three years old. During December, when the rams were 80–100 days old, a brief and transitory peak of prolactin occurred (70 ng PS6/ml plasma ± 10 ng). During each following year, the prolactin level fell in winter to approximately 20 ng/ml. However, in summer the prolactin level was 4 times higher than the winter level during the first year and 11 times higher during the 2nd and 3rd years. A possible role of prolactin variation throughout the breeding season is discussed.
THYROID HORMONE RESPONSE TO VARYING DOSES OF TSH
Authors: Faber Jens , Friis Thorkild , Kirkegaard Carsten , Lauridsen Ulrik Birk , Nerup Jørn , Rogowski Preben , Siersbœk-Nielsen Kaj
Published: December 2008

Fifty-five normal subjects were studied following intravenous injection of increasing doses of bovine thyrotrophin (b-TSH) from 0.5 to 250 mU/kg. Serum triiodothyronine (T3) and thyroxine (T4) were measured 1, 2, 3 and 4 h after the TSH injection. Dose-related increments in serum T3 and T4 were demonstrated with doses of b-TSH = 2.5 mU/kg and a maximum response was obtained after approximately 100 mU/kg. The fractional increase in serum T3 was greater than in serum T4, but the ratio between the increase in serum T4 and serum T3 (21.3/1 ng/ng) was independent of the dose of b-TSH and time after TSH stimulation. The T3 response was reproducible and unaffected by sex and age.
DYNAMIC STUDY OF POST-NATAL THYROID FUNCTION IN THE RAT
Authors: Vigouroux E.
Published: December 2008

The thyroid function in development was investigated in post-natal rats. The thyroid iodine content rapidly increased from birth (137 ± 26 ng iodine/mg thyroid) up to day 10 (338 ± 42 ng iodine/mg thyroid) then increased more slowly up to day 30 (425 ± 34 ng iodine/mg thyroid). The maximal plasma concentration of thyroxine was observed on day 16 (56.9 ± 3.5 ng T4/ml) and of iodide on day 10 (110.2 ± 12.6 ng I−/ml). The turnover rate constant of extrathyroidal thyroxine was higher at birth (8.0 ± 2.3 %/h) than at any older age studied (average 6 %/h). Thyroxine secretion by the thyroid was more intense before weaning (37 ng hormonal iodine/h/100 g body weight on days 10 and 20) than after weaning (22 ± 6 ng hormonal iodine/h/100 g body weight in 30 days old rats). The peripheral deiodination rate of thyroxine represented about 90 % thyroxine secretion rate in newborn and 10 days old rats and only 40% in adult females. In pre-weaning rats, after a single injection of both [131I]L-T4 and [125I]Na, extrathyroidal radioactivity disappeared more slowly than in 30 days old rats and adult animals. This suggests that iodide concentrations of extrathyroidal tissues are higher before than after weaning.
CORTICOSTERONE, 18-OH-DEOXYCORTICOSTERONE, DEOXYCORTICOSTERONE AND ALDOSTERONE SECRETION IN TISSUE CULTURE OF FOETAL RAT ADRENALS IN THE PRESENCE AND THE ABSENCE OF ACTH
Authors: Salmenperä M. , Kahri A. I.
Published: December 2008

A method for simultaneous analysis of the main corticosteroids secreted by the rat adrenal is described. Purification is performed using previously established steps involving dichloromethane extraction, ethanol-cyclohexane partition and Sephadex-LH-20 column chromatography. Deoxycorticosterone and aldosterone are then quantitated with radioimmunoassay and corticosterone and 18-hydroxy-deoxycorticosterone with gas liquid chromatography as their 0-methyloxime-trimethylsilyl ethers. The coefficient of variation of the method for these steroids in concentrations found in the tissue culture of foetal rat adrenals varies between 3.9–10.9%

The secretion of these steroids in the tissue culture of foetal rat adrenals is studied. The steroid secretory pattern is correlated with a differentiation stage of the cultures as detected by electron microscopy. The initial secretory activity declines considerably after 15 days of cultivation to a low level. This is the case also with respect to aldosterone although the cortical cell population changed from the mixed population of the differentiated (zona fasciculata-like) and undifferentiated (zona glomerulosa-like) cells to homogenous undifferentiated growth. Addition of ACTH increased deoxycorticosterone secretion rapidly. Corticosterone, 18-hydroxy-deoxycorticosterone and aldosterone secretion was observed only after the differentiation of the cells (especially changes in their mitochondrial compartment) was evident morphologically.
THE DISTRIBUTION OF BLOOD FLOW TO THE REPRODUCTIVE TRACT OF ANAESTHETIZED EWES NEAR OESTRUS
Authors: Moor R. M. , Bruce N. W.
Published: December 2008

Radioactive microspheres were used to measure the rate and distribution of blood flow to the reproductive tract of anaesthetized sheep. Seven sheep were examined on day 14, 6 on day 15 and 10 on day 16 of the oestrous cycle: oestrus is normally on day 16 or 17. The rate of blood flow to the myometrium, endometrium and oviducts increased by 2-fold from day 14 to 15: the weights of these organs increased on day 16. Blood flow to the vagina and cervix increased by over 10-fold from day 14 to 15 but vaginal and cervical weights remained unchanged.

Thirty minutes after the administration of 1200 IU PMSG, blood flow increased in the vagina and cervix on day 14, the myometrium on day 15 and the vagina, cervix and oviducts on day 16. However, these results must be viewed with caution since there were substantial, though not significant changes in the controls. The results favour the hypothesis that, near the end of the oestrous cycle, oestrogen has a dominant role in the control of blood flow to the reproductive tract of sheep.
CYTOSOL AND NUCLEAR [3H]OESTRADIOL BINDING IN THE FOETAL TISSUES OF GUINEA PIG
Authors: Pasqualini J. R. , Sumida C. , Gelly C.
Published: December 2008

The formation of [3H]oestradiol macromolecule complexes was studied in vivo and in vitro in the kidney, lung and liver of intact foetal guinea pig. Specific binding of [3H]oestradiol was demonstrated in the cytosol and nuclear fractions of foetal kidney. Intensive binding was found in the cytosol of foetal lung but most of the bound radioactive material (71 %) was [3H]oestrone. Some binding was found in the cytosol of foetal liver but not in the nucleus of this tissue.

In the in vivo experiments, the binding of radioactive material to plasma proteins was studied: 22 % of the plasma radioactivity was bound of which 67 % was identified as oestrone sulphate. Oestradiol sulphate represented 7 % and unconjugated oestradiol only 0.6 % (0.1 % of the total plasma radioactivity). On the other hand, 2–3 % of the foetal plasma radioactivity was found as unbound [3H]oestradiol.

In the kidney, the formation of [3H]oestradiol complexes in the cytosol fraction does not depend on temperature while nuclear [3H]oestradiol complexes increase with increasing temperature. Maximal formation of [3H]oestradiol complexes in the cytosol fraction and the 0.1 m TRIS and 0.3 m NaCl nuclear extracts was reached after 15 min but binding in the 1 m NaCl nuclear extract continued to increase up to 30 min.

After incubation of purified nuclei of foetal kidney with 1.1 × 10−7 m [3H]oestradiol, specific binding was found in the different nuclear fractions. Specific binding was also detected in isolated nuclei previously extracted by 0.1 m TRIS and 0.3 m NaCl before being incubated with 1.1 × 10−7 m [3H]oestradiol.

The Kd of binding of [3H]oestradiol in the renal cytosol fraction is 2.5 × 10−10 m with n = 4.5 × 10−14 moles/mg protein. Incubation of isolated 1 m NaCl nuclear extract from foetal kidney with [3H]oestradiol gives a Kd of 3.3 × 10−10 m with n = 2.5 × 10−14 moles/mg protein.

It is concluded that the nuclear complexes in the foetal kidney could be formed either through an intermediate cytosol complex or that the "two step" mechanism could take place in the nucleus. Furthermore, direct binding of [3H]oestradiol with high affinity was observed in the 1 m NaCl nuclear extract.
THE EFFECT OF GONADOTROPHIN RELEASING HORMONE ON PITUITARY-GONADAL FUNCTION IN KLINEFELTER'S SYNDROME
Authors: Smals A. G. H. , Kloppenborg P. W. C. , Lequin R. M. , Benraad Th. J.
Published: December 2008

The mean basal plasma LH and FSH levels in 8 patients with Klinefelter's syndrome were respectively 5 and 15-fold higher than in 8 eugonadal males, whereas plasma testosterone concentration were half the normal value

After an intravenous bolus injection of gonadotrophin releasing hormone (100 μg of LH-RH) the gonadotrophin increase in the Klinefelter patients was more marked than in the control subjects, but in both groups the plasma testosterone levels remained essentially unchanged. In contrast to the bolus injection, an 8 h infusion of LH-RH after the bolus elicited a significant plasma testosterone increase in both the eugonadal males (59%) and the Klinefelter patients (51%).

These findings indicate that despite an impressive endogenous hypergonadotrophism, Leydig cells in Klinefelter's syndrome can still respond to a sustained further increase of these endogenous gonadotrophins and thus still have functional reserve.
TRANSITORY GROWTH HORMONE DEFICIENCY SUCCESSFULLY TREATED WITH HUMAN GROWTH HORMONE
Authors: Trygstad Olav
Published: December 2008

This study was carried out in order to determine whether children with a transitory type of growth hormone deficiency showed an accelerated growth in height velocity on treatment with human growth hormone (HGH).

Following careful diagnostic routine procedures 13 extremely short children were diagnosed as having isolated growth hormone deficiency, and were successfully treated with HGH. A true isolated growth hormone deficiency was present in 5 of the children, whereas 8 showed a normal increase in serum growth hormone on repeated growth hormone stimulation tests after their development of puberty and termination of HGH treatment. Three boys with bone ages of 5.5, 8.0 and 9.5 years showed an undisputable effect following HGH administration. They showed an initial growth at the start of treatment, and a second growth spurt during development of puberty. Two of the boys reached final statures of 14 cm taller than the predicted heights. The other patients, including the children with true isolated growth hormone deficiency showed an initial spurt of growth at the start of the HGH treatment immediately followed by a pubertal growth spurt. The mean acceleration of height velocity for the children with true isolated growth hormone deficiency was from 3.4 cm during the year before treatment to 7.0 cm during the first year on treatment, as compared to 2.8 and 7.4 cm, respectively, for the children with transitory growth hormone deficiency. A girl with severe anorexia nervosa who had a transitory growth hormone deficiency, showed an accelerated high velocity from 1.1 cm to 7.6 cm during the first year following treatment with HGH.

The question whether HGH treatment should be made available to all short children with no known syndrome, and presenting a height less than −3.5 sds, a bone age/chronological age ratio of less than ⅔, and a height velocity less than −2 sds is discussed. The only way to know if a child will respond to HGH treatment is to give it for a trial period of at least six months. At least a physiological stimulus to growth hormone secretion should be decisive in the selection of growth retarded children for HGH treatment. Different mechanisms seem to be responsible for physiological growth hormone secretion to sleep or exercise, and the secretion obtained with pharmacological stimuli.
STIMULATORY EFFECT OF THE DOPA-DECARBOXYLASE INHIBITOR Ro 4-4602 ON PROLACTIN RELEASE; INHIBITION BY L-DOPA, METERGOLINE, METHYSERGIDE AND 2-Br-α-ERGOCRYPTINE
Authors: Pontiroli A. E. , Castegnaro E. , Vettaro M. P. , Viberti G. C. , Pozza G.
Published: December 2008

In order to evaluate the role of serotonin (5-HT) in the effect of L-dopa on prolactin (PRL) release, normal subjects received L-dopa alone or L-dopa plus a dopa-decarboxylase inhibitor (Ro 4-4602) in basal conditions and following the repeated administration of metergoline, a specific anti-5-HT agent. The inhibiting effect of L-dopa on PRL levels was enhanced by metergoline. On the contrary, L-dopa plus Ro 4-4602 induced a sharp increase in serum PRL levels. This effect was completely abolished by metergoline, which also significantly reduced fasting PRL levels in all the subjects studied. Ro 4-4602 alone induced a significant increase in serum PRL levels, similar to that commonly observed with chlorpromazine and TRH. The effect was similar in males and in females and was reproducible in experiments performed on different days. The effect of Ro 4-4602 was completely abolished by 2-Br-α-ergocryptine and metergoline, and, to a lesser degree, was reduced by methysergide. These results suggest that Ro 4-4602 is a reliable stimulus to PRL release and show that any stimulus to PRL secretion may be blocked by both dopa-minergic and anti-serotonin agents.
PLASMA PROLACTIN IN UNDISTURBED CANNULATED MALE RATS; EFFECTS OF PERPHENAZINE, FREQUENT SAMPLING, STRESS AND CASTRATION PLUS OESTRONE TREATMENT
Authors: Mattheij John A. M. , van Pijkeren Thea A.
Published: December 2008

Blood was collected from undisturbed male rats by means of chronically indwelling intrajugular cannulae and the plasma prolactin (PRL) concentration was determined by a radioimmunoassay. The effect of perphenazine, frequent bleeding, handling and brief ether stress in normal males and of stress in castrated oestrone treated males was determined. The plasma PRL concentration in undisturbed intact males was low. Castration plus oestrone treatment for 3 or 7 weeks had little or no effect on the PRL concentration. Neither frequent blood sampling nor removal of 3 ml blood over a period of 5 h affected plasma PRL concentration. Intravenous administration of perphenazine caused a striking and prolonged increase in plasma PRL in intact males. Brief handling or mild ether stress caused a significant rise in PRL within 2 min in intact males; 15–20 min later PRL had returned to the undisturbed level. Brief ether stress in oestrone treated castrates induced a comparable pattern of prolactin release, although of greater magnitude. In these animals a second stress one hour later induced a similar response. It is concluded that chronic cannulation neither affects the unstressed prolactin level nor interferes with the ability of the adenohypophysis to release PRL. The results also indicate that when rats are handled a truly stress free sample can only be obtained when the blood is drawn within one minute after the initial disturbance of the animal. The evidence presented indicates that oestrone treatment increases the responsiveness of male rats to stress-induced PRL release.
THE EFFECT OF EPINEPHRINE AND ISOPROTERENOL ON INSULIN SECRETION AND GLUCOSE UTILIZATION IN ISOLATED ISLETS OF LANGERHANS FROM MICE
Authors: Hermann Leif Sparre , Deckert Torsten
Published: December 2008

The effect of epinephrine and isoproterenol in different concentrations and adrenergic blocking agents on glucose induced insulin secretion and glucose utilization was studied in isolated islets of Langerhans from mice. Epinephrine in physiological concentrations significantly inhibited the glucose induced insulin secretion. This effect was not mediated by a change in glucose utilization but involved α-adrenergic stimulation. Isoproterenol significantly stimulated the glucose induced insulin secretion but had no effect on glucose utilization. β-adrenergic stimulation by isoproterenol at low glucose concentration was not sufficient to stimulate insulin secretion. The results are discussed in relation to current theories on the mechanism of glucose induced insulin secretion.
RELATIONSHIP BETWEEN FOETAL CORTICOSTEROIDS, MATERNAL PROGESTERONE AND PARTURITION IN THE RAT
Authors: Martin C. E. , Cake M. H. , Hartmann P. E. , Cook I. F.
Published: December 2008

The concentration of total corticosteroids, corticosteroid binding globulin (CBG) and progesterone were determined in maternal and foetal/neonatal plasma from rats on days 5, 4, 3, 2, 1 before birth and days 0, 1, and 4 after birth. In addition free corticosteroids and adrenal weight/unit body weight were measured on the foetuses/neonates and the foetuses, respectively. Although the concentration of maternal total corticosteroids and CBG ranged from 53.0 ± 12.5 to 31.0 ± 13.1 μg/100 ml (x̄ ± sem) and 26.6 ± 2.2 to 45.1 ± 0.9 μg corticosteroid bound/100 ml plasma, respectively, the changes in the concentration of these constituents were not related to the initiation of either parturition or lactation. The concentration of total corticosteroids in foetal plasma increased significanly (P < 0.05) from day 5 (14.6 μg/100 ml) to reach peak concentrations (44.9 μg/100 ml) on day 3 before birth and then decreased to low levels (7.7 μg/100 ml) at birth.

The pattern of change in foetal adrenal weight/unit body weight closely followed the pattern of change in the concentration of total corticosteroids in foetal plasma during the last 5 days of gestation. There was a significant (P < 0.05) daily decrease in the concentration of CBG in the foetuses from 4 days before until 1 day before birth, which resulted in a significant (P < 0.01) increase from 3.08 to 5.94 μg/100 ml of free corticosteroids in the foetal plasma between day 2 and day 1 before birth, respectively. This peak corresponded with a significant fall (P < 0.02) in the maternal progesterone (measured by protein binding assay) from 2.57 μg/100 ml to 0.62 μg/100 ml between day 2 and day 1 before birth. Foetal progesterone (measured by radioimmunoassay) showed the same changes as maternal progesterone but was between 25–50 % of that in maternal plasma. These findings suggest that the changes in foetal free corticosteroids and maternal progesterone are important in the initiation of parturition in the rat.
DIURNAL RHYTHM OF 5αANDROST-16-EN-3-ONE AND TESTOSTERONE IN PERIPHERAL PLASMA OF BOARS
Authors: Claus R. , Giménez T.
Published: December 2008

Testosterone and the boar taint steroid 5α-androst-16-en-3-one were determined radioimmunologically in peripheral plasma of 3 boars. A modified extraction procedure for the latter compound was established and its reliability confirmed. Samples of plasma were taken every 30 min during three 48 h periods.

Diurnal rhythms of both steroids were found with maximum values (concentrations > mean + 2 sd) occurring twice daily in the afternoon and after midnight. Corresponding nadirs (concentrations < mean − 2 sd) were found in the early evening and in the morning till around noon. The variations in testosterone were more smooth than those of 5α-androst-16-en-3-one. It is likely that clear cut diurnal rhythms are discernible because of the low base values.
SECRETION OF THYROXINE, 3,5,3′-TRIIODOTHYRONINE AND 3,3′5′-TRIIODOTHYRONINE IN EUTHYROID MAN
Authors: Westgren U. , Melander A. , Ingemansson S. , Burger A. , Tibblin S. , Wa°hlin E.
Published: December 2008

The secretion of iodothyronines from the normal human thyroid gland was assessed by radioimmunoassay analyses of the concentrations of thyroxine (T4), 3,5,3′-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (reverse T3, rT3) in thyroid venous and peripheral venous blood. The subjects studied were euthyroid patients undergoing parathyroid surgery. Measurements were carried out both under apparently normal conditions, following peroral T3 pre-treatment, and before and after acute administration of TSH into a thyroid artery. In the control subjects, significant gradients between thyroid venous and peripheral venous concentrations were recorded both for T4, T3 and rT3, suggesting that all three iodothyronines are secreted by the normal human thyroid. T3 pre-treatment seemed to reduce this secretion, and acute administration of TSH promoted rapid, marked, and concomitant increments in the thyroid venous concentrations of all three iodothyronines. Hence, it appears that not only T4 but also T3 and rT3 are secreted by the normal human thyroid gland, and that TSH stimulates the secretion of all three iodothyronines. On the other hand, calculations of the relative secretion rates yielded the relation T4:T3:rT3 as 85:9:1. This indicates that, in euthyroid subjects, most of T3, and almost all of rT3, is produced by extrathyroidal conversion of T4 and not by direct thyroidal secretion.
BONE MINERALIZATION AND BONE MINERAL CONTENT IN PRIMARY HYPERPARATHYROIDISM
Authors: Tougaard Lars , Hau Christian , Rødbro Paul , Ditzel Jørn
Published: December 2008

The degree of bone mineralization and the bone mineral content (BMC) was evaluated in 6 patients with primary hyperparathyroidism. The degree of bone mineralization was estimated as the phosphorus/hydroxyproline ratio (P/Hypro) in bone biopsies; BMC was estimated by photon absorptiometry on both forearms. The mean values of both parameters were significantly lower than normal (P < 0.001 for P/Hypro; P < 0.02 for BMC). As no significant correlation was found between P/Hypro and BMC in hyperparathyroidism, the findings of low values of P/Hypro and of BMC in patients with elevated serum calcium point to primary hyperparathyroidism.
STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE
Authors: Aedo A. R. , Nuñez M. , Landgren B.-M. , Cekan S. Z. , Diczfalusy E.
Published: December 2008

Circadian variations of the plasma levels of dehydroepiandrosterone, 17-hydroxypregnenolone, pregnenolone and testosterone were investigated by radioimmunoassay in 10 normally menstruating women during the periovulatory period. In seven of the subjects it was also possible to estimate androstenedione and dihydrotestosterone levels. Blood was withdrawn continuously over a period of 48 h at a rate of 4 ml/h by means of a non-thrombogenic pump. The circadian rhythm was studied during 13 3-hour sampling periods (39 h) which were identical in all subjects.

Dehydroepiandrosterone, 17-hydroxypregnenolone and pregnenolone showed a marked circadian rhythm with highest mean levels in the morning between 06.00 and 09.00 h and lowest mean levels during the night between 21.00 and 24.00 h. The peak levels of individual subjects coincided completely with the highest mean levels in the case of dehydroepiandrosterone, in 9 out of 10 cases with regard to 17-hydroxypregnenolone and in 8 of 10 cases as far as pregnenolone levels were concerned. The lowest individual levels were more dispersed around the means than were the individual peaks. The difference between the highest (morning hours: 06.00–09.00) and lowest (evening hours: 21.00–24.00) geometeric mean values was 404% for 17-hydroxypregnenolone, 163 % for dehydroepiandrosterone and 71 % for pregnenolone.

The mean testosterone levels also exhibited an elevation between 06.00 and 09.00 h which was significant (P < 0.05). However, the individual peak values were scattered from 21.00 h of the first day to 18.00 h of the second day. The mean concentrations of androstenedione showed a significant increase between 06.00 and 18.00 h. The individual peaks were widely dispersed. Hence a uniform circadian rhythm correlated to the levels of the Δl5-steroids mentioned above could not be demonstrated in the case of testosterone and androstenedione.

An analysis of variance indicated no significant differences between sampling periods as far as dihydrotestosterone levels were concerned.

The extent and regularity of the circadian variation in the plasma levels of the Δl5-steroids studied makes it mandatory to standardize very carefully the exact time of blood withdrawal in any longitudinal study. In view of the sharp changes in the plasma levels during the morning hours, it is suggested that sampling during the afternoon period may provide more constant values.
CORTISOL AND CORTICOSTERONE PRODUCTIONS OF ISOLATED ADRENAL CELLS IN NEONATAL RABBITS
Authors: Hirose Taeko
Published: December 2008

Isolated adrenal cells of rabbits aged from 0 h to day 40 after birth were incubated for 2 h in the presence of ACTH. Thin-layer chromatography and the fluorimetric method were used to evaluate the products of these adrenal cells separately for cortisol and corticosterone.

Cortisol production by adrenal cells in response to ACTH (0.1 mU) was found to be highest between 0 and 8 h after birth (0.522 ± 0.049 μg/105 cells; mean ± sem). A decrease was observed at 9–20 h and this was further followed by a steady decrease up to day 35–40. Corticosterone production was 0.206 ± 0.042 μg/105 cells between 0 and 8 h after birth. Subsequently, this level was evenly maintained up to day 12–14, but it tended to increase on day 35–40. The level of cortisol production was significantly higher than that of corticosterone production at 0–20 h after birth, while the former was significantly lower than the latter from day 12–14 onwards. The ratio of corticosterone to total corticosteroids (cortisol + corticosterone) was very low (0.28 ± 0.04) at 0–8 h after birth, but showed a progressive rise up to day 35–40, when it was 0.95 ± 0.01. The results of the present study show that cortisol is the pre-dominant product of the adrenal cells in rabbits during early post-natal life.
SERUM PROLACTIN IN PATIENTS WITH "FUNCTIONLESS" CHROMOPHOBE ADENOMAS BEFORE AND AFTER THERAPY
Authors: Samaan N. A. , Leavens M. E. , Jesse J. H.
Published: December 2008

The immunoreactive serum human prolactin (PRL) level was measured before and after intravenous administration of 500 μg of thyrotrophinreleasing hormone (TRH) in 11 patients with "functionless" chromophobe adenomas before and after surgery and after radiotherapy in 6 of these patients. The results were compared to other pituitary function tests. Two of the patients studied had recurrent disease after previous pituitary surgery and radiotherapy.

Five patients had pituitary surgery through the transfrontal route, while 6 had adenoma removal via the transnasal transsphenoidal route.

Before surgery, the serum PRL concentration was abnormally high in 4 patients, before and after TRH administration. It was normal in 6 and subnormal in 1 patient who had had previous therapy. Two of the patients studied showed high serum thyroid-stimulating hormone (TSH) levels in the presence of low serum T3 and T4 suggesting primary hypothyroidism with a secondary TSH-producing pituitary tumour.

After surgery all patients showed a significant decrease of the serum PRL level. This contrasts with more variable results in the measurements of other pituitary hormones. Post-operative radiotherapy produced no significant additional change in serum PRL levels in 5 of the 6 patients measured 6 months to 4 years after radiotherapy. Five of the 6 patients who had adenoma removed via the transsphenoidal route required no cortisol replacement and 4 remained euthyroid, whereas all 5 patients after transfrontal surgery required both cortisol and thyroid hormone replacement.

These results indicate: (1) that measurement of serum PRL levels at basal and after TRH administration in patients with "functionless" chromophobe adenomas before and after treatment may be the best index for evaluating the effect of therapy; (2) that adenoma removal may be followed by preservation of normal pituitary function, but this is more likely to occur if the transsphenoidal approach is used; and (3) that primary thyroid insufficiency may be associated with a pituitary adenoma.
BIOLOGICAL ACTIVITIES OF ACTH-ANALOGUES VARIED IN THE ACTIVE SITE
Authors: van Nispen Johannes W. , Tesser Godefridus I. , Barthe Pierre L. , Maier René , Schenkel-Hulliger Lotte
Published: December 2008

The steroidogenic and lipolytic activities of corticotrophin-(1-24)-tetracosapeptide and [Lys17,18]corticotrophin-(1-18)-octadecapeptide amide were compared with those of corresponding analogues substituted in position 8 with norarginine and homoarginine, and in position 9 with phenylalanine and pentamethylphenylalanine. The norarginine containing analogues demonstrated a rewarding activity, although they were generally somewhat less active than the homoarginine containing compounds. This confirms the previous conclusions concerning the indispensability of arginine as a guanidinium derivate. The analogues in which phenylalanine was a substitute for tryptophan, constituted partial agonists with a low activity in steroidogenesis and lipolysis but a rather high melanophore stimulating activity. Insertion of the permethylated derivative of phenylalanine in this position, which ensures the presence of an aminoacyl residue with the full electron donor properties of tryptophan, destroyed the low steroidogenic and lipolytic activity, but increased the MSH-activity about 2-fold.