bluuebunny/crossref_metadata_2025 huggingface dataset:
A COMPARATIVE STUDY OF SERUM GROWTH HORMONE AND PLASMA CORTISOL LEVELS IN STIMULATION TESTS WITH INSULIN AND PROPRANOLOL-GLUCAGON
Authors: Andler W. , Biro G. , Bernasconi S. , Giovanelli G.
Published: December 2008

Insulin and propranolol-glucagon stimulation tests were carried out on 28 children and 5 adolescents and the results of their growth hormone and plasma cortisol estimations were compared.

Twenty-nine subjects with normal growth hormone reserves showed a mean maximum rise of 17.4 μU/ml of serum growth hormone in the insulin test whereas the intramuscular injection of glucagon after oral premedication with propranolol produced a rise of 38.5 μU/ml. Five subjects with normal growth hormone reserves showed a reduced hormone output in the insulin stimulation tests but normal response in the propranolol-glucagon stimulation tests. Only one subject showed a poor response in the propranolol-glucagon but normal response in the insulin stimulation test.

In 30 subjects with normal adrenocortical function the mean maximum increase of plasma cortisol was 15.6 μU/ml in the insulin – and 14.9 μU/ml in the propranolol-glucagon stimulation tests, respectively. Both methods are suitable for studying the pituitary-adrenocortical interrelationships. The mechanism of the release of glucagon-induced growth hormone is not clear but the fall in blood glucose does not seem to play a major role in the process. A stress-like mechanism is equally unlikely because vegetative symptoms occurred only i a small number of subjects after intramuscular glucagon administration. It is possible that glucagon possesses a releasing-like mechanism which operates in the pituitary itself.
131I-19-IODOCHOLESTEROL SCINTIGRAPHY OF THE ADRENAL CORTEX
Authors: Dige-Petersen H. , Munkner T. , Fogh J. , Blichert-Toft M. , Lund J. O.
Published: December 2008

131I-19-iodocholesterol scintigraphy of the adrenal cortex has been carried out in 26 patients.

In 4 patients with normal adrenocortical function the tracer was equally accumulated on the two sides.

In 7 patients with untreated Cushing's syndrome, bilateral uptake was found in 4 patients with bilateral hyperplasia whereas unilateral visualization was obtained in three cases of cortisol producing adenomas. The side localization was confirmed at operation.

Eight patients had been operated for Cushing's syndrome prior to the scintigraphy. Remnant adrenocortical tissue with negligible or subnormal function (4 patients) could not be visualized. Normo- or hyperfunctioning remnant tissue was visualized in 3 patients. One patient had recurrent hypercorticism due to metastases from a previously removed adrenocortical carcinoma; a single pelvic accumulation was seen, whereas several metastases in the abdomen and thorax were not visualized.

Four patients with aldosteronism were investigated. Three had primary aldosteronism due to an adrenocortical adenoma. In two of these, the site of the adrenal lesion was localized pre-operatively. In the third patient, equal bilateral accumulation of iodocholesterol was seen even after suppression with dexamethasone. At operation a small tumour was found. In 1 patient with indeterminate aldosteronism both glands were visualized and at a second examination the uptake was equally suppressed by dexamethasone.

Finally 3 patients were investigated. One had a testosterone producing tumour of the right ovary. The tumour was not visualized on the scintigram in spite of a slight accumulation of activity as measured in vitro. Another patient with a cyst of the right adrenal gland presented a defect in the activity on the affected side. In the third patient previously subjected to hypophysectomy, the adrenal cortex was visualized only after ACTH-stimulation.

The 131I-19-iodocholesterol scintigraphy is a valuable method for the diagnosis and localization of cortisol and aldosterone producing tumours, and for the localization of normo- and hyperfunctioning adrenocortical remnants. The interpretation of the scintigrams must be based on relevant biochemical assays.
METABOLISM OF [4-14C]PROGESTERONE AND [7α-3H-PREGNENOLONE BY HUMAN OVARIES PERFUSED IN VITRO
Authors: Fukunishi H. , Mickan H. , Zander J.
Published: December 2008

Nine human ovaries were perfused in vitro with [4-14C] progesterone and in addition one ovary with [7-3H] pregnenolone. From the perfusate unchanged progesterone and five different metabolites were isolated: 20α-dihydroprogesterone, 17α-hydroxyprogesterone, 16α-hydroxyprogesterone, 5α-pregnane-3,20-dione and 4-androstene-3,17-dione. In the ovarian tissue saturated pregnane derivatives were the main metabolites.

When [3H] pregnenolone and [14C] progesterone were perfused simultaneously a stimulation of Δ4–5-isomerase and 3β-dehydrogenase activity by HCG was demonstrated.
SUPRASELLAR DISTURBANCE IN THE SYNDROME OF FERTILE EUNUCHOIDISM: CASE REPORT
Authors: del Pozo Emilio , Bolté Edouard , Very Maurice
Published: December 2008

A case of fertile eunuchoidism is presented. The diagnosis was established on the basis of low androgen secretion in the presence of active spermatogenesis, increase in testosterone output after gonadotrophin stimulation, and adequate peripheral response to exogenous testosterone. Resistance to clomiphene stimulation but normal pituitary response to LH-RH was elicited indicating a suprasellar disturbance as the cause of the disorder.
TESTOSTERONE UNDECANOATE: A NEW ORALLY ACTIVE ANDROGEN
Authors: Hirschhäuser C. , Hopkinson C. R. N. , Sturm G. , Coert A.
Published: December 2008

Oral testosterone undecanoate (TU) in arachis oil has been evaluated with a view to its possible use as a means of androgen replacement therapy. A single 100 mg dose was found to elevate plasma androgen levels and urinary 17-ketosteroid excretion in 6 normal men. Ninety mg/day and 60 mg/day doses taken by a hypogonadal man resulted in sustained levels of androgen which appeared physiological when measured by radioimmunoassay without chromatography. However, upon separation of the steroids by chromatography it was found that much of the androgen present was in fact dihydrotestosterone not testosterone. Both TU and dihydrotestosterone undecanoate were detected in plasma by gas chromatography and it is suggested that the ester is absorbed as such from the intestine and the unesterified steroid subsequently released by hydrolysis. The convenience of oral administration, the resulting prolonged elevated plasma androgen levels and the probable lack of deleterious effects on the liver may render oral TU of value where androgen replacement therapy is indicated.
RADIOIMMUNOASSAY OF HUMAN PROLACTIN (PRL)
Authors: Schmidt-Gollwitzer M. , Saxena B. B.
Published: December 2008

A simple and rapid homologous radioimmunoassay of human prolactin (hPRL), by the use of 66% ethanol containing 6.6% ammonium acetate for the separation of free and bound hormones, has been established. PRL levels showed marked individual and daily variations as well as a circadian periodicity in both men and women. Levels of plasma PRL rose with puberty and decreased during post-menopause and in elderly men (ages 60–73 years). There was no marked change in plasma PRL levels at midcycle; however, in some subjects, luteal levels were slightly higher than follicular levels. Administration of oestradiol-17β caused marked increase in plasma PRL levels during menstrual cycle. During pregnancy, the plasma PRL levels rose as high as 200 ng/ml and decreased within a week or two post-partum. During lactation, the levels were higher and increased with suckling. In a patient with habitual abortion, the plasma PRL level showed a sudden drop prior to abortion. Administration of LH-RH had no effect on the secretion of PRL in human subjects.
ADRENAL MEDIATION OF THE EFFECT OF EXCESS ACTH ON TESTOSTERONE LEVELS IN MALE: A STUDY OF A PATIENT WITH PROBABLE ACTH SECRETING MEDULLARY THYROID CARCINOMA
Authors: Hajjar Ridha A. , Hill C. Stratton , Samaan Naguib A.
Published: December 2008

An adult male patient with probable ectopic ACTH production by a medullary carcinoma of the thyroid, was studied before and after bilateral adrenalectomy. Pre-operatively, the patient had low plasma testosterone levels that returned to normal after surgery. The clinical course and study of the patient showed that, 1) chronic excess of ACTH may lower plasma testosterone levels in man, and 2) that this may be mediated through its effect on the adrenals.
STUDIES ON 17β-HYDROXYSTEROID DEHYDROGENASE IN HUMAN ENDOMETRIUM AND ENDOMETRIAL CARCINOMA
Authors: Pollow K. , Lübbert H. , Pollow B.
Published: December 2008

Microsomal 17β-hydroxysteroid dehydrogenase obtained from the human secretory endometrium (17β-HSD) was solubilized with triton X-100. A 4-fold purification was achieved by ammonium sulphate precipitation and isoelectric focusing. In the presence of glycerol the partially purified enzyme was stable at 4°C for at least 48 h.

Using crude microsomes, the conversion of oestradiol to oestrone was linear with time and with the concentration of protein. The optimum temperature was approximately 40°C and the optimum pH 9.4. For the reduction of oestrone the optimum pH was 6.5. With NAD, oestradiol was oxidized approximately three times more rapidly than with NADP. Km-values for oestradiol were nearly the same in endometrial carcinoma and in proliferative and secretory endometrium (i. e. approximately 3 × 10−6 m). The maximal velocity was highest in secretory endometrium.

Testosterone and androstenedione could also serve as substrates but they were interconverted more slowly than oestradiol and oestrone. Sulphhydryl groups were shown to be essential for catalysis.
GLUCOCORTICOID EFFECT ON REPAIR PROCESSES IN VASCULAR CONNECTIVE TISSUE
Authors: Manthorpe R. , Garbarsch C. , Lorenzen I.
Published: December 2008

Male rabbits were injured by a single mechanical dilatation of the aorta and then injected with prednisone 2 mg/kg or saline for 14 days or starved. Morphological studies and biochemical measurements of the collagen metabolism, the content of alpha-amino nitrogen, RNA, DNA, water and fat, and the aorta to serum ratio of 125I-albumin were performed on the intima-media layer of the descending thoracic aorta. Prednisone inhibited the intimal thickening. In the media the infiltration by mononuclear cells, the proliferation and regeneration of the smooth muscle cells and the calcification were reduced.

Prednisone caused a decrease in 0.45 m NaCI soluble collagen as well as in the dialysable and non-dialysable 14C-hydroxyproline fractions. The total amount of collagen, elastin and alpha-amino nitrogen was unchanged, whereas the 14C-proline incorporation in the non-dialysable protein fraction was inhibited to a greater extent than the 14C-hydroxyproline synthesis. The findings indicate that prednisone inhibits the biosynthesis of collagen, which is inhibited to a greater extent than the general protein synthesis. Prednisone increased the dialysable to nondialysable 14C-hydroxyproline ratio consistent with a relative increase in the catabolism of newly synthesized collagen. The aortic content of RNA and DNA was reduced consistent with the inhibition of protein synthesis and cell proliferation. Finally prednisone decreased the aortic content of water when related to the wet weight and increased the aortic content of fat. The aorta to serum ratio of 125I-albumin was not influenced by prednisone.

It is concluded that administration of glucocorticoid for 14 days exerts an inhibitory action on the histological reaction to injury as well as on the biosynthesis of collagen of the repair processes in vascular connective tissue.

A comparison with the effects of prednisone on undamaged rabbit aorta (Manthorpe et al. 1974) demonstrates that the metabolism of collagen of vascular connective tissue during repair is more sensitive to the antianabolic effects of prednisone than collagen in the non-injured aorta. Starvation caused an increase of the aortic percentage of water but otherwise had no influence on the repair processes in the vascular connective tissue.
LIPOATROPHY PRODUCED IN MICE AND RABBITS BY A FRACTION PREPARED FROM THE URINE FROM PATIENTS WITH CONGENITAL GENERALIZED LIPODYSTROPHY
Authors: Foss Irene , Trygstad Olav
Published: December 2008

Urine from 5 patients with congenital generalized lipodystrophy has been fractionated by protein precipitation and Sephadex gel filtration. A fraction with a molecular weight in the range of 1000 was observed to be metabolically active in mice, rats, and rabbits. Hypophysectomized rats got hypoglycaemia following an injection, and the lipolytic-hyperglycaemic effect of ACTH was reduced after injection into intact mice. This effect was probably due to insulin release, because no insulin-like activity was observed on isolated fat cells in vitro. Persistant changes were observed in the animals after 3 weeks of daily injections of the urinary fraction. Adult mice and rabbits developed lipoatrophy with decrease of body weight in spite of a doubling of the food consumption. The metabolic rate and the body temperature were raised. Infantile animals developed a lipodystrophic state with increased growth velocity, and 50 per cent increase of the body weight, although no fat depots were observed. The treated animals got hyperglycaemia, hypertriglyceridaemia, hyperinsulinaemia, and insulin resistance. The rabbits developed manifest diabetes. The corresponding fraction prepared from the urine from the lipoatrophic rabbits produced lipoatrophy after injection into the mice. It is suggested that the lipodystrophic urinary fraction is of hypothalamic origin, and that it acts through the pituitary gland. The fraction is still heterogenous, and was observed to contain thyrotrophin releasing activity.
AN EVALUATION OF THE DIAGNOSTIC VALUE OF SYNTHETIC LUTEINIZING HORMONE RELEASING HORMONE
Authors: Newton John R. , Kilpatrick Michael J. , Pike Janet M. , Collins William P.
Published: December 2008

The potential use of LH-RH as a test of pituitary function in women has been investigated. In this study the synthetic material was administered intravenously, and samples of peripheral blood were removed at defined times. The levels of plasma oestradiol, LH and FSH were determined by radioimmunoassay.

The administration of incremental doses of LH-RH (from 1.56 to 450 μg) demonstrated that a maximal response was obtained with 100 μg in the majority of apparently healthy subjects. Accordingly, this amount was selected as the standard dose for use in a test of pituitary function. The application of this test to 96 patients with secondary amenorrhea showed that the release of LH and FSH (as assessed by the maximum value, and the area under the response curve) was within the normal range in 82, high in 4 and low in 10. There was no correlation between the cause of the amenorrhea, the results of the LH-RH test, and the endogenous levels of oestradiol, LH and FSH.

In addition 5 patients with primary amenorrhea and 8 patients with pituitary disorders were tested with LH-RH. In primary amenorrhea low basal levels of LH were found, but all subjects had a normal response to LH-RH. In 3 patients with clinical hypopituitarism the basal levels of gonadotrophins were in the normal range, but there was an impaired response to LH-RH.

It is concluded that 100 μg of LH-RH administered intravenously may be used to test the ability of the pituitary to release LH and FSH, but the magnitude and duration of the response is not of additional diagnostic value.
RADIOIMMUNOASSAY OF [8-ARGININE]-VASOPRESSIN
Authors: Czernichow P. , Merkelbach U. , Vallotton M. B.
Published: December 2008

A radioimmunological method for the determination of the human antidiuretic hormone, [8-arginine]-vasopressin (AVP), is described in detail. The antiserum has been raised in rabbits injected with AVP adsorbed onto charcoal particles and is used at a final dilution of 1:200 000. It contains antibodies directed specifically against the C-terminal tripeptide and possesses a high association constant of 8.2× 1012 1/mole. AVP is labelled in monoiodinated form (as proven after pronase digestion) at a high specific activity close to the theoretical maximum after purification from unlabelled hormone on Sephadex gel. The standard curves are characterized by a Bo of 55 %, a limit of detection ascertained at least at 3 pg (10 % displacement) and a 50 % displacement achieved with 35.5 pg. The index of precision λ ranges from 0.033 to 0.042. The conditions of the assay (buffer's composition and pH, timing) were systematically varied and tested. In addition the result of immunization of chicken with AVP is reported. The assay is adequate for the measurement of AVP in urine and plasma and will be described in forthcoming papers.
EFFECTS OF HYPOTHYROIDISM AND THYROXINE SUBSTITUTION ON THE METABOLISM OF L-METHIONINE, L-CYSTATHIONINE AND TAURINE IN DEVELOPING RAT BRAIN
Authors: Heinonen Kirsti
Published: December 2008

In hypothyroidism induced by radioiodine the activity of cystathionine synthase and the concentration of L-cystathionine in cerebrum and cerebellum of developing rat decreased markedly. The amount of taurine was significantly higher in cerebral and cerebellar tissue of hypothyroid rats than in corresponding parts of normal rat brain. Early substitution therapy with L-thyroxine corrected these changes.
ACTION OF GROWTH-PROMOTING HORMONES ON MACROMOLECULAR BIOSYNTHESIS DURING LOBULO-ALVEOLAR DEVELOPMENT OF THE ENTIRE MAMMARY GLAND IN ORGAN CULTURE
Authors: Mehta Rajendra G. , Banerjee Mihir R.
Published: December 2008

The entire 2nd thoracic mammary gland of the immature virgin BALB/c mouse was stimulated to full lobulo-alveolar (LA) growth after 120 h organ culture in hormone supplemented medium. The minimal hormonal combination required was insulin (I) + prolactin (Prl) + aldosterone (A). The corticosteroid was replaceable by oestradiol-17β (E) + progesterone (P). The combination I alone or I + the steroid hormone(s) failed to induce the LA development and similar results were also evident in presence of Prl + the steroids. Incubation of the glands in medium with I + Prl + A activated a sequential rise of RNA, protein and DNA synthesis. A near maximal increase of RNA synthesis was present at 48 h in the medium with I + Prl, addition of the steroid hormones did not show further stimulatory effect. Supplementation of the medium with I + Prl and the adrenal or the ovarian steroids was needed for maximal activation of protein synthesis at 72 h and DNA replication at 96 h. The medium with I alone did not show a substantial rise of macromolecular biosynthesis in the mammary gland in organ culture. The highest level of DNA polymerase activity was observed at 72 h in glands cultivated in medium with I + Prl and A or E + P. Only a modest increase of DNA polymerase activity was present in glands cultivated with I alone or I + Prl. Prior treatment of the glands (cultivated with I + Prl + A) with actinomycin D or puromycin resulted into 44 and 40 % reduction of DNA polymerase activity suggesting hormone-induced synthesis of the enzyme before the rise of DNA synthesis in the mammary cells at 96 h in organ culture. Significance of these results with respect to the action of the "growth-promoting" hormones in the mammary gland in organ culture and in the animal has been discussed.
VARIATIONS IN THE CONCENTRATION OF TESTOSTERONE IN PERIPHERAL VENOUS PLASMA FROM HEALTHY WOMEN
Authors: Tyler John P. P. , Newton John R. , Collins William P.
Published: December 2008

The concentration of testosterone (ng/100 ml; mean ± sd) has been determined in peripheral venous plasma at 4 hourly intervals for 24 h from 9 non-pregnant women (39.8 ± 11.8) and 9 during late pregnancy (70 ± 32). In addition, the level of this hormone has been measured in samples of plasma removed daily (between 08.30 and 10.00 h) throughout 9 ovarian cycles (41.6 ± 11.8), and weekly from 10 women during gestation (57.6 ± 14.7).

The results show that there is considerable individual variation in both the concentration and pattern in serial samples over the respective time scales. The values of the arithmetic mean from non-pregnant subjects show that there is a tendency for the concentration to be lower between 20.00 and 04.00 h. However, the differences between the values at defined times over a 24 h period are not statistically significant. During the ovarian cycle 3 subjects had peak values during the peri-ovulatory phase, 2 in the luteal, 1 in the follicular and 3 showed no consistent pattern. There was no significant difference in values (40.9 ± 11.8, 41.9 ± 11.9 and 41.8 ± 11.9) for the 3 phases of the cycle. There is a significant rise in the concentration of plasma testosterone during pregnancy (P< 0.0005), but the pattern of the arithmetic mean is not related to the corresponding values for progesterone or oestradiol. During late pregnancy (34 weeks to term) there is a change in the nycterohemeral pattern, with the highest mean values occurring between 16.00 and 04.00 h. The results are discussed.
PROGESTERONE, 20α-DIHYDROPROGESTERONE AND 20β-DIHYDROPROGESTERONE IN MOTHER AND CHILD AT BIRTH
Authors: Runnebaum B. , Stöber I. , Zander J.
Published: December 2008

In 14 healthy pregnant women at term progesterone (P) and 20α-dihydroprogesterone (20α-DHP) were determined by radioimmunoassay both in the maternal and foetal compartments. The average concentrations were as follows (ng/ml blood or ng/g wet weight tissue): peripheral maternal blood P 56 ± 26, 20α-DHP 16 ± 8; placental tissue P 2514 ± 1516, 20α-DHP 429 ± 412; placental blood P 365 ± 160, 20α-DHP 35 ± 18; blood of the umbilical vein P 388 ± 121, 20α-DHP 33 ± 15; blood of the umbilical arteries P 162 ± 62, 20α-DHP 28 ± 10.

In 5 healthy pregnant women at term progesterone (P), 20α-dihydroprogesterone (20α-DHP) and 20β-dihydroprogesterone (20β-DHP) were also determined by gas-liquid chromatography both in the maternal and foetal compartments. The average concentrations were as follows (ng/ml plasma or ng/g wet weight tissue): peripheral maternal plasma P 129 ± 49, 20α-DHP 15 ± 15, 20β-DHP 1.7 ± 0.9; placental tissue P 5060 ± 1435, 20α-DHP 230 ± 158, 20β-DHP 38 ± 30; placental plasma P 723 ± 245, 20α-DHP 24 ± 13, 20β-DHP 1.0 ± 0.1; plasma of the umbilical vein P 704 ± 227, 20α-DHP 17 ± 3, 20β-DHP 1.2 ± 0.3; plasma of the umbilical arteries P 324 ± 94, 20α-DHP 17 ± 5, 20β-DHP 2.6 ± 2.1

These results show that, contrary to the progesterone concentrations, no significant difference exists in the concentrations of 20α-DHP and 20β-DHP between the blood from the umbilical vein and arteries. Furthermore, no significant difference could be found in the concentrations of P and 20α-DHP between the sexes in either the blood from the umbilical vein or from the umbilical arteries.
THE EFFECT OF ARTIFICIAL CRYPTORCHIDISM ON SERUM OESTROGEN AND TESTOSTERONE LEVELS IN THE ADULT MALE RAT
Authors: Hall R. W. , Gomes W. R.
Published: December 2008

Oestrone, oestradiol and testosterone levels were measured by radioimmunoassay in male rats 0.5, 1, 4, 8 and 16 days after rats were either made artificially cryptorchid or sham-operated. Oestradiol levels were not significantly different between cryptorchid and control rats 12 h or 1 day after surgery, but levels in cryptorchid animals fell to 35 % of controls on day 4 (P < 0.05), 31% on day 8, and 29% on day 16 (P < 0.01). Conversely, oestrone and the total of the two oestrogens was higher in cryptorchid rats at one-half day (P <0.05), but did not differ at any other time. Testosterone levels were generally lower in cryptorchid rats than in controls. The minor contribution of oestradiol to total oestrogen levels and the lack of change of total oestrogens in cryptorchid rats led to the conclusion that oestrogens are probably not the tubular regulator of FSH in the male.
METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS
Authors: Szalay R. , Krieg M. , Schmidt H. , Voigt K. D.
Published: December 2008

In order to get more information on the mode of action of anti-androgens, two series with low but biologically active doses of cyproterone acetate were started. In the first experiments 12 μg of [3H] cyproterone acetate was injected intravenously into adult rats castrated 3 days before treatment. Thirty min after injection the radioactivity uptake in the target organs and other tissues was measured. The metabolites were separated by thin layer chromatography. A large pool of radioactivity could be shown in the liver. Thin layer chromatography revealed that in this pool cyproterone acetate had been converted by more than 80% to one metabolite. In blood plasma, too, the metabolite accounted for the major part of radioactivity. When compared to skeletal muscle, the prostate, seminal vesicles, and m. bulbocavernosus and m. levator ani accumulated more radioactivity. Within 30 min unchanged cyproterone acetate was retained selectively thus showing its relative high affinity to target organs. In a second experimental series, adult castrated male rats were given 10 μg of cyproterone acetate intravenously 30 min before the injection of [3H] testosterone or [3H]5α-dihydrotestosterone. Under this condition androgen uptake in target tissues was reduced to about 70 % of the control values. The data parallel the results of in vivo studies on cytosol receptor displacement of androgens by cyproterone acetate. In agreement with previous investigators no significant influence of the anti-androgen on androgen metabolism was observed. The importance of the findings concerning the mode of anti-androgen action is discussed.
THE EFFECT OF DIFFERENT DOSES OF OESTRADIOL-17β ON COLLAGEN SYNTHESIS IN THE FEMUR OF CASTRATED FEMALE RATS
Authors: Langeland Norvald
Published: December 2008

The effect of different doses of oestradiol-17β on collagen metabolism in the femur of castrated young mature female rats was studied. The animals received daily injections of the hormone for 21 days and 25 μCi [14C]proline was injected intraperitoneally 24 h before the rats were sacrificed.

The rats receiving 1 μg oestradiol per day had a significantly higher specific activity of hydroxyproline in bone compared to the normal and the castrated control rats. At the same time the bone weights and collagen content per femur were less in the rats receiving oestradiol 1 and 2 μg/day than in the control animals. The higher specific activity of bone hydroxyproline in the rats receiving oestradiol-17β 1 μg/day did not, however, indicate a higher bone collagen accretion rate. As all rats received the same amount of [14C] proline, and the body weights differed considerably at sacrifice, the animals probably had different tissue fluid concentrations of [14C] proline. This possibility was supported by the observation that serum concentrations of radioactivity were inversely correlated to body weights. "Correcting" for differences in body weights, the castrated control rats turned out to be the group with the highest specific activity. On doses of 10 and 20 μg oestradiol-17β per day, the specific activity of hydroxyproline in bone was lower than in the control rats while bone weights and collagen content of the femur were not different from the corresponding values of the castrated controls. This finding suggests a "slow down" of collagen metabolism – both with regard to the accretion and the resorption.

At high doses – 10 and 20 μg oestradiol per animal per day – the percentage of incorporated 14C found as [14C]hydroxproline was reduced. The reason for this altered total-C14/[14C]hydroxyproline ratio is at present unknown.
ASSESSMENT OF GONADOTROPHIN SECRETION IN WOMEN WITH ANOREXIA NERVOSA
Authors: Aono T. , Kinugasa T. , Yamamoto T. , Miyake A. , Kurachi K.
Published: December 2008

The LH and FSH secretions in 21 patients with anorexia nervosa were assessed by radioimmunoassay. On a single iv injection of 100 μg LH-releasing hormone (LH-RH), 8 patients showed LH response comparable to that of normal cyclic women in the follicular phase, and 5 patients showed excessive response. Although the remaining 8 patients showed almost no LH response, infusion of 400 μg LH-RH or daily im injections of LH-RH restored gonadotrophin responsiveness to LH-RH in all patients tested.

The initial rise in LH during clomiphene citrate treatment was observed in 3 out of 5 patients, but the second peak of LH was found in only one patient. The initial suppression of LH following iv injection of conjugated oestrogen (Premarin®) was observed in 9 out of 10 patients but a rebound increase comparable to that in normal cyclic women in the mid-follicular phase was found in only 3 patients.

These results seem to suggest that impaired hypothalamic function is the cause of gonadotrophin deficiency and the resultant anovulation in most patients with anorexia nervosa.
THE EFFECTS OF DEXAMETHASONE AND STARVATION ON BODY COMPOSITION AND REGIONAL ADIPOSE TISSUE CELLULARITY IN THE RAT
Authors: Krotkiewski Marcin , Björntorp Per
Published: December 2008

In order to examine regional effects of corticosteroids on the depot fat distribution a dose of dexamethasone that produced changes in fat cell weight (40 μg per kg per day) was administered to rats. Starved rats were included for comparison.

Starvation caused a decrease in depot fat and fat cell weight proportional to the characteristic fat cell weight of that region. In comparison with the changes found in the depots of pair-fed rats the effects of dexamethasone in this dose were largely the same. The epididymal adipocytes behaved differently and were emptied more slowly than their weight indicated.
OESTRADIOL RECEPTOR LEVELS IN THE HUMAN FALLOPIAN TUBE DURING THE MENSTRUAL CYCLE
Authors: Robertson D. M. , Landgren B.-M. , Guerrero R.
Published: December 2008

The levels of cytoplasmic high-affinity oestradiol receptor sites were determined in the isthmus, isthmus-ampulla, ampulla and fimbria of human Fallopian tubes obtained from 23 women during the proliferative and secretory phase of the menstrual cycle and after menopause. Each segment was homogenized in 0.25 m sucrose and fractionated by differential centrifugation into an 800 g × 15 min nuclear pellet and a 100 000 g×1 h cytoplasmic supernatant and pellet. The nuclear and cytoplasmic pellets were extracted with 0.01 m Tris/HCl pH 8.0 containing 0.25 m sucrose, 1 mM EDTA and 0.1 m KCl. The receptor levels were determined in the 100 000 g × 1 h supernatant (free receptors) and in the KCI extracts (bound receptors). Values are expressed per μg DNA.

The concentration of receptors (total, free and bound) was significantly greater in the ampulla than in the isthmus in both phases of the menstrual cycle (P < 0.001). The concentration of free receptors in the isthmus, isthmus-ampulla and ampulla obtained in the proliferative phase was not significantly different from that of the secretory phase. In the fimbria a significantly higher concentration (P < 0.01) was observed in the proliferative phase. The bound receptors were significantly higher in all regions in the proliferative phase than in the secretory phase (P < 0.01).

As a consequence the concentration of total receptors was significantly greater along the tube in the proliferative phase (P < 0.01). The levels of oestradiol in the nuclear pellet of each segment as measured by radioimmunoassay were significantly greater in the isthmic region (P < 0.01) than in other regions of the tube. The inverse relationship between the concentration of oestradiol receptor sites and the nuclear levels of oestradiol along the Fallopian tube is discussed.
METABOLISM OF OESTRADIOL-17β AND OESTRONE IN THE HUMAN UTERUS
Authors: Krishnan A. R. , Bajaj B. K. , Hingorani V. , Laumas K. R.
Published: December 2008

A study of the metabolism of oestradiol in the human endometrium and myometrium of the proliferative and secretory phases of the cycle showed that the conversion of oestradiol to oestrone by endometrium in the proliferative phase was higher than that in the secretory phase. The decreased metabolic activity of the secretory phase endometrium was attributed to the influence of progesterone on the endometrium. The metabolic conversion of oestradiol to oestrone was enhanced when pyridine nucleotides were added to the system. The conversion of oestradiol to oestrone was maximum in the cytoplasmic and nuclear fractions of the endometrium. Furthermore, the conversion of oestradiol was low in all the subcellular fractions of the myometrium as compared with the endometrial subcellular fractions. The presence of co-factors increased the metabolic conversion of oestradiol to oestrone in the subcellular fractions of the endometrium. The presence of 17β-hydroxysteroid oxidoreductase was indicated in all the subcellular fractions. A correlation was found between the amount of oestradiol and oestrone bound to the receptors in the uterus and the rate of metabolism of oestradiol in the uterus. The physiological significance of metabolism of oestradiol and the hormone action are discussed.
GROWTH HORMONE RELEASE FOLLOWING THYROTROPHIN-RELEASING HORMONE INJECTION INTO PATIENTS WITH ANOREXIA NERVOSA
Authors: Maeda K. , Kato Y. , Yamaguchi N. , Chihara K. , Ohgo S. , Iwasaki Y. , Yoshimoto Y. , Moridera K. , Kuromaru S. , Imura H.
Published: December 2008

The effect of thyrotrophin-releasing hormone (TRH) or luteinizing hormone-releasing hormone (LH-RH) on plasma levels of growth hormone (GH), prolactin (PRL), thyrotrophin (TSH), and luteinizing hormone (LH), were studied in patients with anorexia nervosa. The basal plasma GH levels were elevated in 6 of 11 patients studied. Intravenous injection of synthetic TRH (500 μg) significantly raised the plasma GH levels in 9 of 11 patients. The peak values of plasma GH after TRH ranged from 6.0 to 31.5 ng/ml. Plasma GH concentrations also increased following the administration of synthetic LH-RH (100μg) in 1 of 7 patients. The intravenous injection of saline solution caused no significant change in plasma GH in these patients. The plasma LH responses to LH-RH were significantly blunted in all patients, whereas the plasma PRL and TSH responses to TRH were almost normal in the patients examined. These results suggest that the hypothalamo-pituitary function regulating GH and LH secretion is altered in patients with anorexia nervosa.
NON-SUPPRESSIBLE INSULIN-LIKE ACTIVITY AND SULPHATION ACTIVITY IN SERUM EXTRACTS OF NORMAL SUBJECTS, ACROMEGALICS AND PITUITARY DWARFS
Authors: Schlumpf U. , Heimann R. , Zapf J. , Froesch E. R.
Published: December 2008

Non-suppressible insulin-like activity (NSILA) is a term used for a variety of substances in serum, excluding insulin, which promote glucose uptake of adipose tissue and diaphragm in vitro. NSILA-S is a peptide with a molecular weight of 7000 which is soluble in acid ethanol and which has been purified on a large scale from human serum.

This study describes a simple chromatographic one step procedure by which NSILA-S can be extracted and quantitatively measured in individual sera. Using Sephadex G-75 equilibrated with 1 m acetic acid, NSILA-S was detected only in one peak containing small molecular peptides. NSILA-S obtained with this one step chromatographic procedure exerted all the effects of purified NSILA-S including sulphation activity on the rat cartilage. All chromatographic fractions with NSILA-S also had sulphation activity.

Both, NSILA-S and sulphation activity were increased in acromegalics and decreased in pituitary dwarfs. It is suggested that one molecule in serum is responsible for both activities which are, at least in part, under the control of growth hormone.
EFFECT OF ACTINOMYCIN D ON THE PITUITARY RESPONSE TO LH-RH
Authors: Vilchez-Martinez Jesus A. , Arimura Akira , Schally Andrew V.
Published: December 2008

The effect of Actinomycin D (Act D) on the release of LH and FSH induced by LH-RH was investigated in rats. Immature male rats received an iv infusion over a period of 3–4 h or a quick iv injection of synthetic LH-RH. Infusion of LH-RH significantly increased serum LH and FSH levels at 1, 2, 3 and 4 h after the initiation of infusion. Pre-treatment with 100 μg/100 g b. w. Act D failed to affect the rise of serum LH and FSH levels 1 h after the infusion but significantly suppressed the response at 2, 3 and 4 h. The increase in serum LH and FSH levels after a quick injection of LH-RH was unaffected by pre-treatment with Act D whether the antibiotic was injected 1 or 2 h before LH-RH. The results suggest that the initial phase of the pituitary response to LH-RH does not require DNA-dependent RNA synthesis, whereas that in the later period does. RNA synthesis may be necessary only to maintain the increased secretion of both LH and FSH during a continuous stimulation with LH-RH.
ALDOSTERONE SECRETION DURING HIGH SODIUM CEREBROSPINAL FLUID PERFUSION OF THE BRAIN VENTRICLES
Authors: Abraham Suzanne F. , Blair-West John R. , Coghlan John P. , Denton Derek A. , Mouw David R. , Scoggins Bruce A.
Published: December 2008

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n = 5) received perfusion with artificial CSF containing Na 170 mEq./l, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./l, Group III (n = 7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 ± 7.4 to 8.6 ± 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in blood aldosterone in Group II but this was not significant until 4 h post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.
PATHWAYS OF TESTOSTERONE SYNTHESIS IN DECAPSULATED TESTES OF MICE
Authors: de la Torre B. , Benagiano G. , Diczfalusy E.
Published: December 2008

In order to study the temporal relations in the biogenesis of testosterone, decapsulated testes of adult mice were incubated with carbon-14-labelled sodium acetate and attempts were made to isolate the most likely intermediates.

Considerable quantities of radiochemically homogeneous squalene, lanosterol, cholesterol, testosterone and androstenedione, but no pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone sulphate or dehydroepiandrosterone sulphate were isolated. The same pattern of incorporation was found when gradually increasing amounts of non-labelled pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate or testosterone were added to the system as "trapping agents" or when Leydig cell preparations rather than decapsulated testes were used.

The presence of 10 mIU of HCG greatly enhanced the de novo formation of testosterone, androstenedione and 5α-dihydrotestosterone but did not change the pattern of acetate incorporation.

Radioimmunoassays of the incubation medium with or without added HCG, and carried out at different periods of time indicated the presence of gradually increasing amounts of testosterone and androstenedione together with some 5α-dihydrotestosterone, whereas only trace amounts of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone and dehydroepiandrosterone were present.

An analysis of the incubated testes revealed that the addition of HCG significantly enhanced the content of testosterone, androstenedione and 5α-dihydrotestosterone. Little or no increase was observed as far as pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone or dehydroepiandrosterone were concerned.

It is concluded that decapsulated testes of mice synthesize de novo testosterone from sodium acetate under conditions in which the formation of pregnenolone, progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone sulphate and 17-hydroxypregnenolone sulphate cannot be demonstrated.
A HISTOCHEMICAL APPROACH TO THE STUDY OF HUMAN CHORIONIC GONADOTROPHIN RECEPTORS IN THE RAT TESTIS
Authors: Lago A. Dal , Rolandi M. T. , Galli S. , Bortolussi M.
Published: December 2008

Standard suspensions of interstitial cells in PBS were exposed to the action of various fixatives, solvents (clearing agents), temperatures and U. V. light, in order to establish the effects of such chemical and physical agents on the HCG receptors. After exposure to the various agents, the interstitial cells were incubated with [125I]HCG for 2 h at 37°C. To check the specificity of the reaction, competitive tests were performed with added excess non-iodinated HCG.

Only formaldehyde fixation for short periods of time, preserved satisfactorily the specific binding activity of the receptors.

A different degree of thermolability of the receptors was demonstrated, in relation to 37, 45, 54 and 60°C, while freezing in liquid nitrogen had no effect on the receptors binding activity.

After the binding reaction, solvents had a significant solubilizing effect on the HCG-receptor complexes.

U. V. light had no significant damaging effect on the receptors.

The application of the results for a histochemical approach to the study of the HCG receptors is discussed.
A SIMPLE COMPETITIVE PROTEIN-BINDING ASSAY FOR ADENOSINE-3′,5′-MONOPHOSPHATE IN PLASMA AND URINE
Authors: Madsen S. Nistrup , Badawi I. , Skovsted L.
Published: December 2008

A modified competitive protein-binding assay for the measurement of adenosine-3′,5′-monophosphate is desribed. The procedure allows measurement of adenosine-3′,5′-monophosphate in unextracted plasma samples. The mean plasma values in 25 normal, fasting and ambulatory subjects were 22.7 ± 4.7 pmol/ml (mean ± sd) (range 13–31 pmol/ml. The mean urinary content was 3.2 ± 1.0 μmol per g creatinine (mean ± sd) (n=24).
EFFECT OF α-MSH ON PLASMA LEVELS OF LH, FSH, PROGESTERONE AND CORTISOL DURING THE CORPUS LUTEUM PHASE OF THE MENSTRUAL CYCLE
Authors: Runnebaum B. , Heep J. , Geiger W. , Vecsei P. , Andor J.
Published: December 2008

In healthy women (21–28 years) the influence of synthetic α-MSH upon the peripheral plasma levels of LH, FSH, progesterone and cortisol was determined during the corpus luteum phase of the menstrual cycle. As controls 3 women were given 6 intravenous infusions of 250 ml NaCl; 4 women received a total of 18 intravenous infusions of 5–20 mg α-MSH from 9.00 to 11.00 a. m. on the 5th and 7th hyperthermic day of the menstrual cycle. The blood levels of the hormones were usually followed for 24 h, and in two cases for 48 h. During and after the control as well as the experimental infusions with 5–20 mg α-MSH, no significant changes in the plasma concentrations of LH, FSH and progesterone were found. The cortisol concentrations, however, showed on the average a 2-fold increase over the initial values during the infusion of 5 mg and 10 mg α-MSH. During the control infusions they were not enhanced. One experiment was conducted with 20 mg α-MSH. The increase in the plasma cortisol levels following α-MSH administration generally seemed to be dose dependent, but statistically no significant differences regarding the increase in cortisol level could be detected between the 5 mg and 10 mg doses.
SOME ASPECTS OF HYPOTHALAMIC-PITUITARY FUNCTION IN PATIENTS WITH ANOREXIA NERVOSA
Authors: Travaglini P. , Beck-Peccoz P. , Ferrari C. , Ambrosi B. , Paracchi A. , Severgnini A. , Spada A. , Faglia G.
Published: December 2008

The secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotrophin (TSH) and prolactin (PRL, was studied in 17 women suffering from anorexia nervosa. The mean basal serum LH was reduced (8.4 ± 0.8 se mIU/ml; P < 0.001 vs normal controls), while LH increase after gonadotrophin-releasing hormone (LH-RH) appeared to be normal in 9 cases and impaired in 6 cases. The mean basal FSH did not significantly differ from normal subjects (3.9 ± 0.5 mIU/ml), while LH-RH administration elicited an exaggerated increase in 7 cases and a normal increase in 8 cases: the mean FSH response was significantly higher than in controls (P < 0.02). Plasma oestradiol-17β was reduced (20.4 ± 0.4 pg/ml; P < 0.001) while the serum testosterone levels were normal (0.73 ± 0.09 ng/ml). Clomiphene administration induced an increase in gonadotrophins in only 1 out of 7 patients. The mean serum TSH concentration was normal (2.3 ± 0.4 μU/ml), while serum thyroxine and triiodothyronine and free thyroxine index, though generally in the normal range, were significantly lower than values obtained in a control group (6.1 ± 0.4 μg/100 ml, P< 0.005; 102.3±7.7 ng/100 ml, P <0.005; 3.8±0.3, P < 0.05). Though the mean serum TSH increase after thyrotrophin-releasing hormone (TRH) was normal (12.0 ± 2.3 μU/ml), there were 4 impaired and 1 exaggerated increases, and 8 patients showed a delayed and frequently prolonged response.

The increase in serum T3 after TRH appeared lower than in normal subjects (36.3 ± 1.8 ng/100 ml, P < 0.001). Serum PRL levels in basal conditions were higher than in the controls (19.4 ± 4.1 ng/ml, P < 0.001) while the increase in PRL after TRH was exaggerated in only 2 patients. The present data suggest that the primary failure in gonadotrophin secretion in anorexia nervosa occurs at hypothalamic level; moreover the data on TSH and PRL secretion also point to the existence of a hypothalamic disorder in this disease.
THE EFFECT OF ACTH ON PLASMA TESTOSTERONE AND ANDROSTENEDIONE CONCENTRATIONS IN PATIENTS WITH PROSTATIC CARCINOMA
Authors: Cowley Teresa H. , Brownsey B. G. , Harper M. E. , Peeling W. B. , Griffiths K.
Published: December 2008

The effect of Synacthen (β1–24-corticotrophin) on plasma testosterone and 4-androstene-3,17-dione concentrations in untreated patients with prostatic carcinoma, and in patients receiving endocrine therapy is described. An established specific radioimmunoassay was used for the measurement of testosterone, and a radioimmunoassay for 3-androstene-3,17-dione using thin layer chromatography has been developed. Administration of Synacthen resulted in a fall in testosterone in untreated patients, but a rise in 4-androstene-3,17-dione was observed. The plasma concentration of testosterone in all treated patients increased after administration of Synacthen. An increased concentration of plasma 4-androstene-3,17-dione was also observed in these treated patients after Synacthen, but the magnitude of the response was not significantly different from that of untreated patients.

The work provides further evidence that in the patient being treated with oestrogen for carcinoma of the prostate a rise in plasma testosterone concentration will result from an increased secretion of ACTH.
PLASMA CONCENTRATION OF OESTRADIOL-17β IN PREMATURE THELARCHE AND IN DIFFERENT TYPES OF SEXUAL PRECOCITY
Authors: Escobar Maria Eugenia , Rivarola Marco A. , Bergadá César
Published: December 2008

Plasma Oe2 concentration was measured by radioimmunoassay in patients with premature thelarche, with precocious puberty and in 29 normal controls. The mean plasma Oe2 was 1.5 pg/ml (0–7.2) in normal prepubertal girls, 23.8 ± 17.8 (sd) in pubertal girls, 50.2 (± 19.4) in the follicular phase, and 94.2 (± 19.5) in the luteal phase of normal adult females. Ten girls with premature thelarche had a mean of 7.7 ± 6.6 pg/ml. Three of them showed higher values than the other 7, suggesting that in these cases, elevated levels of plasma Oe2 might have played a role in the development of breast tissue. Ten untreated girls with idiopathic precocious sexual development had a mean of 51.6 ± 42.9 pg/ml while 6 patients treated with 150 mg per week of medroxyprogesterone acetate had a mean of 11.4 ± 2.5 pg/ml. Two patients with Down's syndrome, hypothyroidism and sexual precocity had plasma Oe2 of 144 and 31.5 which fell to 24.7 and 8 pg/ml, respectively, after thyroid replacement. One girl with a granulosa cell tumour had a basal value of 304 pg/ml and a concentration of 27 pg/ml after surgery.