bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON A HUMAN CHORIONIC GONADOTROPHIN-LIKE MATERIAL PRESENT IN NON-PREGNANT SUBJECTS
Authors: Robertson D. M. , Suginami H. , Montes H. Hernandez , Puri C. P. , Choi S. K. , Diczfalusy E.
Published: December 2008

The presence of an hCG-like material in urinary and pituitary extracts and plasma obtained from non-pregnant subjects was investigated. Two assay methods were used to detect this material following fractionation of pituitary and urinary extracts by gel filtration (Ultrogel AcA 54) and/or isoelectrofocusing: a) a radioimmunoassay employing an antiserum raised against a specific sequence of the carboxy terminal region (residues 115– 145) of the β-subunit of hCG, and b) an in vitro bioassay method which measures both hLH and hCG activities. The fractionation procedures employed provide a satisfactory separation of highly purified hCG and hLH preparations.

In the pituitary and urinary extracts hCGβ-peptide-like immunoactive (PIA) material was found consistently, which co-eluted with iodinated hCG following gel filtration and possessed pI values similar to those of hCG when subjected to isoelectrofocusing. The PIA material also exhibited in vitro biological activity similar to that shown by hLH and hCG. Detectable levels of immunoactive material were also found in plasma; however, the plasma levels of this PIA material were not influenced by classical endocrine measures such as the stimulation or inhibition of gonadotrophin secretion. The low levels of this material in plasma precluded its further characterization by gel filtration or electrofocusing.

Whereas the present data and those reported by other investigators seem to suggest the presence of some hCG-like material in urinary and pituitary extracts and possibly in plasma of non-pregnant subjects, it is emphasized that the available evidence is not sufficiently conclusive to exclude other interpretations as to the nature of this material.
ULTRASTRUCTURAL MORPHOMETRY OF SPARSELY GRANULATED PROLACTIN CELL ADENOMAS OF THE HUMAN PITUITARY
Authors: McComb D. J. , Kovacs K.
Published: December 2008

Fifteen sparsely granulated prolactin-producing adenomas and 10 non-tumourous adenohypophyses, removed by surgical hypophysectomy, have been studied using morphometry at the electron microscopic level. Compared to non-tumourous prolactin cells, sparsely granulated adenomatous prolactin cells showed a significant decrease in diameter and volume density of secretory granules and an increased volume density of rough-surfaced endoplasmic reticulum and Golgi apparatus. The volume density of mitochondria remained unchanged. These results indicate that the cells of the adenoma are in a highly active functional state. It appears that the equilibrium between hormone synthesis, storage and release is altered in adenomatous prolactin cells.
PRIMARY ALDOSTERONISM: INABILITY TO DIFFERENTIATE UNILATERAL FROM BILATERAL ADRENAL LESIONS BY VARIOUS ROUTINE CLINICAL AND LABORATORY DATA AND BY PERIPHERAL PLASMA ALDOSTERONE
Authors: Vetter H. , Siebenschein R. , Studer A. , Witassek F. , Furrer J. , Glänzer K. , Siegenthaler W. , Vetter W.
Published: December 2008

In 31 patients with primary aldosteronism routine clinical and laboratory data, the effect of orthostasis on plasma aldosterone (PA), plasma renin activity (PRA) and cortisol (PC), effect of fludrocortisone or high sodium intake on basal PA and night-day fluctuations of basal PA and PC with and without suppression of pituitary ACTH by dexamethasone were determined to differentiate patients with a unilateral aldosterone producing tumour (adenoma, APA, n = 20; carcinoma, CA, n = 1) from those with idiopathic bilateral adrenal hyperplasia (IAH, n = 10).

Mean systolic and diastolic blood pressure, age, serum sodium, serum potassium and urinary excretion of sodium and potassium were not significantly different in both groups of patients. Normokalaemic primary aldosteronism occurred both in patients with APA (n = 2) and in patients with IAH (n = 1). Mean basal PA and mean urinary excretion rate of aldosterone-18-glucuronide were higher though not significantly different in patients with APA or CA than in those with IAH. A substantial number of the patients with APA (n = 5) and with IAH (n = 3) showed urinary excretion rates of aldosterone-18-glucuronide ≦ 13 μg/24 h.

Mean PA and PRA significantly increased (P < 0.025) in patients with IAH in response to posture. However, these changes also occurred at times in some patients with APA.

Both fludrocortisone and high sodium intake produced a variable and no group-specific effect on basal PA.

Night-day variations in PA were positively correlated with those in PC in all patients with APA (n= 12) and in 5 of 8 patients with IAH. A dissociation of PA and PC, however, was only observed in patients with IAH. Finally, the effect of dexamethasone on plasma aldosterone curves was variable in both groups of patients.

Our results indicate that under the described conditions analysis of routine clinical and laboratory data and of peripheral PA, PRA and PC are of limited value in differentiating patients with APA or CA from those with IAH.
CHOLINERGIC INFLUENCES ON HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL ACTIVITY OF STRESSED RATS: AN APPROACH UTILIZING CHOLINE DEFICIENT DIETS
Authors: Sithichoke N. , Malasanos L. J. , Marotta S. F.
Published: December 2008

Male rats were placed on choline (Ch) deficient diets for 3 to 14 days, without and with Ch (normal and large doses) supplemented in the drinking water, to determine whether altering the availability of Ch would affect the cholinergic system in relation to the latter's role in modulating the hypothalamic-pituitary-adrenocortical (HPA) system of non-stressed and stressed animals. The results indicate that the basal nonstressed activity of the HPA system, as assessed by adrenal and plasma corticosterone concentrations, was not affected by placing the animals on these diets for as long as 14 days. Furthermore, the in vitro production of corticosterone by these adrenal glands, in the presence or absence of adrenocorticotrophin, was similar to those observed in animals on a regular rat diet; however, the HPA responses to auditory (100 db) stress, and to a lesser extent hypercapnic (9 % CO2) stress, were impaired on the Ch deficient diet (14 days), and these responses were partially corrected by supplementing the diet with Ch in the drinking water. Thus, the data suggest that altering the dietary intake of Ch may affect cholinergic activity, which in turn affects the HPA response to stressors.
HORMONAL AND ULTRASTRUCTURAL OBSERVATIONS IN A CASE OF RESISTANT OVARY SYNDROME
Authors: Starup J. , Pedersen H.
Published: December 2008

This report describes in detail the hormonal and ultrastructural findings in a 21 year old woman with secondary amenorrhoea. who fulfilled all the criteria necessary to establish the diagnosis of resistant ovary syndrome. Ovarian biopsies revealed numerous primordial and primary follicles, which both by light and electron microscopy showed a normal morphology. Nevertheless, the follicles could not be stimulated neither by large doses of human gonadotrophins alone nor by simultaneous administration of cortisone acetate and large doses of human gonadotrophins. The association of a decreased target cell response with increased levels of serum FSH and LH might be explained in different ways. The presence of an inhibitor preventing the normal action of gonadotrophins could not be substantiated, because we did not detect any circulating gonadotrophin antibodies. Furthermore the serum prolactin level was normal.
KIDNEY FUNCTION IN NORMAL MAN DURING SHORT-TERM GROWTH HORMONE INFUSION
Authors: Parving H.-H. , Noer I. , Mogensen C. E. , Svendsen P. Aa.
Published: December 2008

Kidney function was studied in 9 normal males before and during a 2 h growth hormone (GH) infusion of 50 ng/kg/min. The following variables were measured during each 20 min clearance period: glomerular filtration rate, GFR, effective renal plasma flow, RPF (steady state infusion technique with urinary collections using [125I]iothalamate and [131I]iodohippurate), and urinary albumin and β2-microglobulin excretion rates (radioimmunoassays).

The GH infusion resulted in a 10-fold increase in plasma GH concentration.

All the above mentioned variables remained practically unchanged during the infusion except for a small (−5%) but significant decrease in renal plasma flow (P < 0.01). Our negative results contrast to the findings of increased GFR and RPF during prolonged GH administration and suggest that GH requires several hours or days for its renal effects to become manifest.
IMMUNOREACTIVE β-MSH IN HUMAN PLASMA AND IN A CORTICOTROPHIC ADENOMA CULTURE MEDIUM. ITS RELATION TO THE LIPOTROPHINS
Authors: Bertagna X. , Donnadieu M. , Seurin D. , Binoux M. , Girard F.
Published: December 2008

In order to characterize more accurately the relationship between immunoreactive β-MSH ("β-MSH") and the lipotrophins (LPH) we attempted to investigate the gel filtration and the immunological characteristics of "β-MSH" in the plasma of patients with Nelson's syndrome and Addison's disease as well as in the culture medium from a human corticotrophic adenoma using a sensitive radioimmunoassay from human β-MSH.

When added either to hormone free plasma or to a plasma from a patient with Nelson's syndrome all the human β-MSH (hβ-MSH) elutes from a Sephadex G-50 column as a single peak in a volume corresponding to its molecular weight. In contrast plasma "β-MSH" in 3 patients with Nelson's syndrome and one patient with Addison's disease almost completely elutes in a volume corresponding to a molecular weight range of 6000– 10 000; no "β-MSH" can be detected in its normal elution volume. Drastic pH change (8.2 to 2.3) does not significantly alter the elution pattern. Chromatography of a corticotrophic adenoma culture medium gave a similar pattern of "β-MSH" with a main peak in the molecular weight range of 6000–10 000. In our radioimmunoassay the culture medium and purified hβ-LPH gave parallel displacement curves for [125I]hβ-MSH. It is suggested that hβ-LPH or a closely related substance is the main material responsible for "β-MSH" immunoactivity.
EFFECT OF CLOMIFENE ON THYROID FUNCTION IN NORMAL MEN
Authors: Feldt-Rasmussen Ulla , Lange Axel P. , Date John , Hansen Mogens Kern
Published: December 2008

To study the effect on thyroid function 100 mg of clomifene citrate was given once a day to two groups of healthy male volunteers for 5 and 12 consecutive days, respectively.

In both groups serum concentrations of TSH, thyroxine, triiodothyronine, T3 resin uptake test and thyroid hormone binding proteins were measured before, during and after oral administration of clomifene. The effect of clomifene treatment was evaluated in Group 1 by means of serum FSH and LH measurements. Further in Group 2 the serum TSH response to iv TRH (200 μg) was also investigated.

The mean per cent elevations in serum concentrations of FSH and LH were 145 and 200, respectively. In Group 1 a small but statistically significant decrease within reference limits in triiodothyronine (P < 0.01) and free thyroxine index (P < 0.02) was found on day 4 of clomifene. On day 5 a slight increase in TSH was observed (P < 0.05). In Group 2 the response of TSH to TRH showed a non-significant increase after 5 days and a significant increase (P < 0.01) after 12 days of clomifene. Eight days after discontinuation of the drug the response was restored to normal. No changes in the thyroid hormone binding proteins in serum could be demonstrated. Though the observed changes were slight, they indicate that clomifene exerts an influence directly on the thyroid function.
RENAL HANDLING OF HOMOLOGOUS RADIOIODINATED THYROTROPHIN IN THE RAT
Authors: Kuku S. F. , Kjeld M. , Gunasekera S. W. , Diamant L. , Fraser T. R.
Published: December 2008

Previously, TSH metabolism and tissue distribution in the rat were studied using heterologous hormone and/or unphysiological doses. We injected iv [131T]rTSH (S.A. 100 μCi/μg) in physiological doses (10 ng) to KI blocked male rats. Two to 180 min after which TCA precipitable 131I was measured in the kidney, liver, muscle, fat and testis. The highest TCA precipitable radioactivity concentration, peak value 12 % at 30 min; organ/blood ratio, 16, was found in the kidney. With the kidney validated as the major site of localization of TSH, the renal localization and handling of [125I]rTSH was studied by autoradiography. Radioactivity was confined to the cortex. Two to 30 min samples showed 125I in Bowman's space and luminal parts of the proximal tubular cells while samples from 60 to 180 min revealed activity in contraluminal areas, suggesting glomerular filtration and tubular re-absorption. Gel-filtration of supernatants of kidney homogenates revealed progressive diminution of the TSH peak and the appearance of a smaller MW peak. We conclude that (1) the kidney is the major site of localization and metabolism of homologous TSH, (2) the renal handling of TSH involves both glomerular filtration and tubular re-absorption.
A METHODOLOGICAL STUDY IN MEASURING T3 AND T4 CONCENTRATION IN RED AND WHITE SKELETAL MUSCLE AND PLASMA OF EUTHYROID RATS
Authors: Janssen J. W. , van Hardeveld C. , Kassenaar A. A. H.
Published: December 2008

T3 and T4 concentrations were determined in plasma and red and white skeletal muscle of the rat. Because of the small tissue samples (± 300 mg), the ultra-sensitive Wick radioimmunoassay (RIA) for serum was adapted for determination in ethanol extracts.

The dilution curves of the plasma and tissue extracts showed excellent parallelism with the standard curves for both T3 and T4.

The mean T4 level found in female rats (n = 6) was 22.6 ± 5.2 ng/ml in plasma and did not differ significantly between red (1.85 ± 0.28 ng/g) and white (1.90 ± 0.25 ng/g) skeletal muscle.

The mean T3 level in 11 normal female rats was 0.629 ± 0.098 ng/ml in the plasma and was significantly higher in the red muscle (2.07 ± 0.26 ng/g) than in the white muscle (1.65 ± 0.20 ng/g).

The higher T3 levels found in the red muscle as compared with the white muscle may help to elucidate the different responsiveness of these muscle types observed in altered thyroid states.
STEROID EXCRETION IN ANOREXIA NERVOSA PATIENTS
Authors: Vanluchene E. , Aertsens W. , Vandekerckhove D.
Published: December 2008

Seven anorexia nervosa (A. N.) patients had reduced urinary excretion values of tetrahydrocortisone (THE), androsterone (A) and 5α-tetrahydrocortisol (5α-THF). THE to tetrahydrocortisol (THF), A to aetiocholanolone (Ae) and 5α-THF to THF ratios were all significantly reduced. Six A. N. patients had oral metyrapone tests with quantitatively normal but delayed urinary 3α,17α,21-trihydroxy-5β-pregnan-20-one (THS) response.

The steroid determinations were done by capillary gaschromatography, which proves to be of value in the study of the above mentioned metabolic abnormalities.
THE DYNAMICS OF GROWTH HORMONE AND PROLACTIN SECRETION IN ACROMEGALIC PATIENTS WITH "MIXED" PITUITARY TUMOURS
Authors: Lamberts Steven W. J. , Klijn Jan G. M. , Kwa Giok H. , Birkenhäger Jan C.
Published: December 2008

The dynamics of growth hormone (GH) and prolactin (PRL) secretion in response to thyrotrophin-releasing hormone (TRH) and bromocriptine were evaluated in 15 untreated and 1 previously unsuccessfully treated patients with acromegaly. In 7 of these patients elevated basal PRL levels were found.

In 4 of the 7 hyperprolactinaemic patients plasma PRL concentrations followed closely the pattern of GH secretion in response to TRH (400 μg). The maximal paradoxical increment of GH in response to TRH was paralleled by a delayed PRL response, while a close relationship was observed between the suppression of the elevated GH and PRL levels in these patients after one single dose of 2.5 mg bromocriptine. In one of these patients parallel escapes of plasma GH and PRL during bromocriptine treatment were seen. In addition, a significant higher sensitivity to the GH-lowering effect of 2.5 mg bromocriptine was noted from 2 up to 8 h in these 4 patients with presumably "mixed" GH/PRL secreting pituitary adenomas, compared with the response in 9 untreated acromegalic patients with normal basal PRL levels. In the 3 acromegalic patients with slightly elevated PRL levels, no or a normal increase of PRL levels in response to TRH was observed, while the suppressive effect of bromocriptine on plasma GH concentrations was not different from that seen in the acromegalic patients with normal PRL levels. However, as a group the 7 patients with hyperprolactinaemia showed a significantly higher GH-lowering effect to 2.5 mg bromocriptine than the 9 normoprolactinaemic acromegalic patients.

A close relationship between the magnitude of the increment of GH in response to TRH and the decrease of plasma GH after 2.5 mg bromocriptine was present in the whole group of 16 acromegalics (P < 0.01). No such correlation was shown in the type of response of plasma GH to an oral glucose load or the coefficient of variation of basal plasma GH levels on 5 different days.

It is concluded that in the population of acromegalic patients with elevated plasma PRL levels a sub-population of patients is present with "mixed" pituitary adenomas which secrete GH and PRL in a parallel manner. The characteristics of the secretion of both hormones, in these patients can be recognized as a parallel, delayed response of both hormones to TRH and an increased sensitivity to the suppressive effect of bromocriptine.
STUDIES OF THE TSH RADIORECEPTOR ASSAY
Authors: Beall Gildon N. , Chopra Inder J. , Solomon David H. , Irvine W. James , Kruger Sally R.
Published: December 2008

We have examined several variables in the reagents and procedures used in the TSH radioreceptor assay, the binding of iodinated TSH to its thyroidal receptor. We found that iodinated bovine TSH (S.A. 30 U/mg) was more effectively bound to receptor than iodinated human TSH (S.A. 7.3 U/mg). Iodination of TSH with the Bolton-Hunter acylation method apparently prevented binding to TSH receptor. Surgically removed human thyroid tissue specifically bound 10.3 ±1.0 (mean ± sem) of added [125I]TSH, but post-mortem human thyroid bound only 3.9 ± 0.4% of [125I]TSH (P< 0.001). Maximal binding of [125I]TSH was found at pH 5.8. Many tissue preparations contained activity, possibly due to proteases, which inactivated TSH, and inclusion of a protease inhibitor, aprotinin, significantly increased specific binding.
THYROID AND ADRENOMEDULLARY REACTIONS DURING SLEEP DEPRIVATION
Authors: Palmblad Jan , Äkerstedt Torbjörn , Fröberg Jan , Melander Arne , von Schenck Henning
Published: December 2008

The possible influence of a 48 h period of sleep deprivation on the serum concentrations of total and unbound 3,5,3′,5′-thyroxine (T4) and 3,5,3′-triiodothyronine (T3), and of total 3,3′,5′-triiodothyronine (reverse T3, rT3) was studied in 12 young male volunteers. In addition, plasma concentrations of TSH and the urinary excretion of noradrenaline and adrenaline were examined. Both total S-T4, S-T3 and S-rT3, and unbound S-T4 and S-T3 (unbound rT3 was not calculated) were significantly enhanced following sleep deprivation. P-TSH showed a numerical but statistically not significant increase, while the catecholamines remained unaltered. The results suggest that sleep deprivation provokes enhanced secretion of thyroid hormone(s), supposedly via increased secretion of TSH.
ONTOGENY AND DISTRIBUTION OF IMMUNOREACTIVE GASTRIC INHIBITORY POLYPEPTIDE (IR-GIP) IN RAT SMALL INTESTINE
Authors: Gespach C. , Bataille D. , Jarrousse C. , Rosselin G.
Published: December 2008

The ontogeny and distribution of immunoreactive gastric inhibitory polypeptide (IR-GIP) has been studied in the rat duodenum and jejunoileum between day 20 post-coitum and day 150 post-partum by radioimmunoassay following tissue extraction. In foetuses on day 20 of gestation, the content of IR-GIP was 2.0 ± 0.2 ng/duodenum and 18 ± 2.0 ng/jejuno-ileum. The IR-GIP content increased during the whole period investigated and a peak of concentration was observed in the first post-natal week in both the duodenum (860 ± 150 ng/g) and jejunoileum (650 ± 135 ng/g). In the duodenum, the main increase in IR-GIP content (ng per organ) occurred in the 3rd week of life and the same phenomenon was observed 2 weeks later in the jejuno-ileum. The highest GIP concentration was found in the duodenum and in the proximal jejunum, indicating that the upper small intestine is the major site of IR-GIP storage. It is concluded that the ontogeny of IR-GIP further supports the concept that this hormone is involved in the endocrine regulation of metabolism and suggests that this regulatory process takes place at an early stage of rat development.
THE CONCENTRATIONS OF URINARY OESTRONE-3-GLUCURONIDE, LH AND PREGNANEDIOL-3α-GLUCURONIDE AS INDICES OF OVARIAN FUNCTION
Authors: Collins W. P. , Collins P. O. , Kilpatrick M. J. , Manning P. A. , Pike J. M. , Tyler J. P. P.
Published: December 2008

Methods based upon the principles of radioimmunoassay have been developed and evaluated for the measurement of oestrone-3-glucuronide, LH and pregnanediol-3α-glucuronide in samples of unextracted urine. The procedures have been applied to daily urine (early morning fraction and combined 24 hour collections) from 6 women throughout one complete menstrual cycle and to serial samples from an additional 14 women who only collected early morning specimens.

The results showed that there were characteristic, well-defined changes in the concentration of all 3 metabolites in both samples of urine and from all subjects. In addition, there was a reasonable correlation between the concentration of all 3 compounds in samples of early morning urine and the corresponding rates of excretion per 24 hours. These findings suggest that the procedures may be of value for monitoring ovarian function over long periods of time, without the problems of stress and inconvenience to the patient. Furthermore, the ratio of values for oestrone-3-glucuronide to pregnanediol-3α-glucuronide may be used to indicate the start and finish of the fertile period.
TISSUE CULTURE STUDIES ON HUMAN PITUITARY TUMOURS: LONG TERM RELEASE OF ANTERIOR PITUITARY HORMONES INTO THE CULTURE MEDIUM
Authors: Lipson Loren G. , Beitins Inese Z. , Kornblith Paul L. , McArthur Janet W. , Friesen Henry G. , Kliman Bernard , Kjellberg Raymond N.
Published: December 2008

A study was undertaken to determine the length of time that human pituitary tumours are capable of releasing anterior pituitary polypeptide hormones in vitro under basal conditions and to study the spectrum of hormone release by functioning and "non-functioning" pituitary neoplasms. Fragments from the pituitary tumours of 10 patients in the following categories: 1 Cushing's disease, 2 with amenorrhoea-galactorrhoea, 3 with acromegaly, and 4 with "non-functioning" pituitary tumours and from 2 normal human anterior pituitary glands were placed in primary culture immediately after surgery. The in vitro release of human growth hormone (hGH), prolactin (Prl), thyrotrophin (TSH), adrenocorticotrophin (ACTH), luteinizing hormone (LH), and follicle stimulating hormone (FSH) was measured by specific radioimmunoassays at the end of each week in culture. Hormone release was surveyed from 6 weeks to 6 months depending upon the survival of the culture. Hormone release patterns were compared with clinical and pathological data.

In the initial week of the study, all 6 anterior pituitary polypeptides were detected in the media from the 2 control pituitaries and from 4 of the tumours (1 amenorrhoea-galactorrhoea and 3 acromegaly) in concentrations up to 100 ng/ml of medium while 5 of the 6 hormones were readily detectable in the media from 2 additional tumour samples (Cushing's disease and 1 "non-functioning" pituitary tumour). The media of the remaining 4 tumours contained at least 3 of the 6 hormones (1 amenorrhoea-galactorrhoea and 3 "non-functioning" pituitary tumours). After 6 months in culture, the 6 hormones were readily detectable in at least 1 of the 5 surviving cultures and hGH (up to 800 ng/ml) and LH were each detectable in the media from 2 cultures. Although most of the hormone concentrations in the media decreased with length of time in culture, there were 2 exceptions. First, in the media from 5 of the 12 cultures from both controls and tumours, Prl concentrations increased after 50 to 80 days culture. This increase usually lasted for several weeks before Prl levels again began to decline. The second unusual finding occurred in a tumour from a patient with acromegaly in the media of which hGH levels rose from 60 ng/ml to 800 ng/ml between days 125 and 174.

These findings of prolonged hormone release in vitro give promise of future usefulness of tissue culture methods for study of polypeptide hormone releasing mechanisms and long-term production of human anterior pituitary hormones for use in research and possible therapy.
BONE MINERAL LOSS IN INSULIN-TREATED DIABETES MELLITUS: STUDIES ON PATHOGENESIS
Authors: McNair P. , Madsbad S. , Christensen M. S. , Christiansen C. , Faber O. K. , Binder C. , Transbøl I.
Published: December 2008

To elucidate pathogenetic factors of bone mineral loss in diabetes mellitus, bone mineral content (BMC), glucose and calcium homeostasis were evaluated in a cross-sectional study of 215 insulin-treated diabetics.

BMC declined 10% during the first 5 years of diabetes. This coincided with cessation of insulin secretion, deterioration of metabolic control and raising urinary excretion rates of calcium and phoshorus. BMC was inversely correlated to fasting blood glucose (P < 0.02), to glycosuria (P < 0.02) and to insulin requirement (P < 0.002), and positively to the glucagon-stimulated serum C-peptide levels (P < 0.005). Urinary excretion rates of calcium and phosphorus correlated positively with the degree of hyperglycaemia (P < 0.001) and glycosuria (P <0.001). The skeletal calcium loss corresponded to the excess of urinary calcium excretion during the phase of BMC reduction. There was no evidence of secondary hyperparathyroidism.

The relationship between bone loss and disturbed glucose homeostasis indicates that diabetic bone loss is secondary to the metabolic abnormalities, possibly acting directly on bone.
17α-HYDROXYLASE DEFICIENCY. A COMBINATION OF HYDROXYLATION DEFECT AND REVERSIBLE BLOCKADE IN ALDOSTERONE BIOSYNTHESIS
Authors: Rovner D. R. , Conn J. W. , Cohen E. L. , Berlinger F. G. , Kern D. C. , Gordon D. L.
Published: December 2008

We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17α-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days.

Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17α-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone.

We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.
PARTIAL PURIFICATION AND CHARACTERIZATION OF A BINDING PROTEIN FOR INSULIN-LIKE ACTIVITY (ILAs) IN HUMAN AMNIOTIC FLUID: A POSSIBLE INHIBITOR OF INSULIN-LIKE ACTIVITY
Authors: Drop Stenvert L. S. , Valiquette Guy , Guyda Harvey J. , Corvol Maité T. , Posner Barry I.
Published: December 2008

An insulin radioreceptor assay (INS-RRA) and an insulin-like activity radioreceptor assay (ILAs-RRA) have been utilized to partially purify and characterize a protein from human amniotic fluid with ILAs-RRA reactivity. An acid-ethanol soluble protein with an apparent molecular weight of 34 500 daltons by calibrated Sephadex chromatography and an isoelectric point (pI) of 4.7 accounts for all of the ILAs-RRA reactivity present in human amniotic fluid. Since this protein has been found to be a binding protein for ILAs. but not for insulin, it has been termed amniotic fluid binding protein or AFBP. AFBP is reactive in a non-parallel manner in the ILAs-RRA and totally inactive in the INS-RRA. The activity of AFBP in the ILAs-RRA is thus to the competition of AFBP with the placental membrane receptor for the [125I]ILAs tracer employed in the ILAs-RRA.

AFBP inhibits the activity of added ILAs, but not of added insulin, in the INS-RRA, presumably by binding ILAs, while being inactive itself. In two biological assays studied to date, the rat epididymal fat pad assay and the rabbit chondrocyte sulphation assay, AFBP also inhibits the activity of added ILAs. These observations raise the possibility that binding protein(s) for insulin-like peptides may function as inhibitors of their bioactivity in different physiologic and pathologic states. The relation of AFBP to binding protein(s) in human plasma remains to be clarified.
CIRCADIAN RHYTHM OF FREE OESTRADIOL IN RELATION TO PLASMA CORTISOL IN LATE HUMAN PREGNANCY
Authors: Reck G. , Noss U. , Breckwoldt M.
Published: December 2008

The present study investigates the diurnal variations of free plasma oestradiol levels in late human pregnancy. The oestradiol levels are correlated to the maternal adrenal function as reflected by the plasma levels of cortisol.

According to the half life time of oestradiol, blood samples were collected at short time intervals of 30 and 60 min, respectively. Three pregnant women volunteered in the study.

Free oestradiol was measured by radioimmunoassay and cortisol was quantitated by a protein binding method.

All patients exhibited a circadian rhythm for free oestradiol with significantly higher values in the early morning (28.3 ± 7.2 ng/ml) than in the afternoon and early night (21.2 ± 3.6 ng/ml, P < 0.001). The course of oestradiol followed in a moderate but significant correlation plasma cortisol (r = 0.34, P < 0.001). During the period of increasing cortisol the oestradiol levels demonstrated the phenomenon of episodic secretion.

The results obtained suggest that the maternal adrenals predominantly regulate the diurnal rhythm of free oestradiol in late human pregnancy.
RESPONSE OF PLASMA NON-CONJUGATED OESTRADIOL TO MANIPULATED ADRENAL FUNCTION BY ACTH AND DEXAMETHASONE
Authors: Reck G. , Noss U. , Breckwoldt M.
Published: December 2008

The present study is concerned with the regulation of free plasma oestradiol in relation to maternal adrenal function during late human pregnancy. Blood was collected in 9 patients at short time intervals of 30 min from 17 h to 3 h. In order to exclude endogenous ACTH-secretion 5 patients received 12 mg dexamethasone over 48 h. Between 20 h and 2 h 0.25 mg ACTH1-24 (Synacthen°) was infused into the subjects. Nonconjugated oestradiol was determined by radioimmunoassay and total plasma cortisol by protein binding method.

During the application of ACTH free oestradiol increased from 21.3 ± 5.7 to 25.5 ± 7.1 ng/ml (P < 0.025) in the patients without dexamethasone. The increase was moderately correlated to rising cortisol (r = 0.58, P < 0.001). Plasma oestradiol reached its maximum level after 90 min, followed by a tendency to decline despite persisting stimulation of maternal adrenals.

The patients receiving dexamethasone exhibited during ACTH-infusion a rise of oestradiol from 3.8 ± 1.9 to 7.8 ± 3.1 ng/ml (P < 0.001). Increasing oestradiol was strongly correlated to plasma cortisol (r = 0.67, P < 0.001). The phenomenon of earlier declining oestradiol levels did not occur. These results suggest that maternal adrenals predominantly regulate the formation of free oestradiol. Plasma cortisol indicating maternal precursor production balances the increase of oestradiol by suppressing foetal precursor supply.
SECRETION OF PROTEINS, ANDROGEN BINDING PROTEIN AND OESTRADIOL BY SERTOLI CELLS IN CULTURE: EFFECTS OF SERUM
Authors: Rommerts F. F. G. , Krüger-Sewnarian B. C. , Grootegoed J. A. , de Jong F. H. , van der Molen H. J.
Published: December 2008

Effects of chicken- and foetal calf serum on secretion products of Sertoli cells have been investigated. At day 5 or 6 of culture, Sertoli cells incubated with 1 % chicken serum secreted significantly more androgen binding protein (ABP) than cells cultured in media without chicken serum. This effect of chicken serum was smaller than that of chicken serum together with FSH and testosterone. Addition of 1 % chicken serum or foetal calf serum stimulated the incorporation of [3H] leucine in secreted proteins by Sertoli cells. Secretion of oestradiol-17β (Oe2) was stimulated by addition of foetal calf serum. However, chicken serum did not stimulate the secretion of Oe2 even in the presence of extra added testosterone. The nature of the compounds in the sera responsible for these effects is unknown, but the effects cannot simply be explained by the presence of FSH or androgens. The results indicate that compounds other than FSH and androgens may influence Sertoli cell function. Evidence has been obtained that a serum component with a molecular weight of less than 5000 may be involved in the stimulation of Oe2 production.
WORK CAPACITY, CONTRACTILE PROTEIN AND QUANTITATIVE ELECTROMYOGRAM (EMG) CHANGES FOLLOWING EXERCISE OR NANDROLONE DECANOATE TREATMENT IN EXPERIMENTALLY INDUCED MUSCLE DISUSE ATROPHY IN RATS
Authors: Madena-Pyrgaki A. , Pappas C. , Deligiannis A. , Apostolakis M.
Published: December 2008

Anabolic steroid administration and planned exercise have been the two main methods applied to improve the function and morphology of atrophied muscle tissue. The effects of these two factors-specifically nandrolone decanoate administration and exercise by swimming on muscle weight, EMG activity, work capacity and on contractile protein content of rat gastrocnemius muscle, following experimentally induced atrophy by immobilization, were investigated. The results appear to support the conclusion that although both types of treatment obtain significant positive results exercise acts more effectively than the anabolic steroid in this respect.
BIOLOGICALLY ACTIVE LUTEINIZING HORMONE (LH) IN PLASMA
Authors: Bártfai G. , Robertson D. M. , Diczfalusy E.
Published: December 2008

A comparison was made between an in vitro bioassay method and a radioimmunoassay (RIA) method for the assay of LH activity of male plasma. The in vitro bioassay was based on the LH-stimulated production of testosterone by interstitial cells obtained from mouse testes. The RIA procedure consisted of a non-equilibrium procedure employing an antiserum with high specificity and a well characterized iodinated hLH tracer. A highly purified hLH preparation (hLH 1st IRP imm.) was used as standard with both procedures.

Parallel line assays were performed with both methods on 36–38 plasma samples obtained over a 24 hour period from each of 7 normal male subjects. Significantly higher concentrations of bioactivity than immunoactivity were obtained with a biological: immunological (B/I) ratio for all subjects of 1.56 (1.34: 1.78) (geometric mean and 95% confidence limits in brackets). A regression analysis of the two activities for each subject indicated a close correlation (r = 0.90) and the 95% confidence limits of the regression line intercept obtained from all subjects included the origin. However, significant differences between subjects were observed with regard to the B/I ratios and regression coefficients.

A comparison of the B/I ratio for male plasma (1.56 (1.34: 1.78)) with that of a highly purified hLH preparation (1.39 (1.34: 1.44) suggests that the elevated ratios found in male plasma are in part attributable to the presence in the standard preparation of relatively high levels of immunologically active material which is biologically inactive. If so, a reference preparation with higher purity would result in more similar values of biological and immunological activity.

From this study it is concluded that with the use of suitable assay methods a close relationship can be shown between the biological and immunological activities in male plasma. However, the significance of the differences in the B/I ratios and the regression coefficients observed requires continued investigation.
CALCIUM AND PANCREATIC β-CELL FUNCTION
Authors: Hellman Bo
Published: December 2008

Glucose is believed to stimulate incorporation of calcium into the secretory granules of the pancreatic β-cells. The mechanism of the glucose-stimulated accumulation of calcium in the granule pool was evaluated by measuring fluxes of 45Ca in β-cell-rich pancreatic islets microdissected from ob/ob-mice. The incorporation of lanthanum-nondisplaceable 45Ca in response to glucose differed from both the basal uptake and that seen in response to phosphate in being suppressed by 10 μm antimycin A, 0.3 mm 2,4-dinitrophenol or 1 mm N-ethylmaleimide. Exposure to each of these metabolic inhibitors also resulted in a protracted efflux of the glucose-sensitive 45Ca under conditions when neither the 45Ca incorporated in the presence of 3 mm glucose nor in response to phosphate was significantly affected. The glucose-stimulated intracellular 45Ca existed in a state allowing it to be washed out with the ionophore A-23187. The results suggest that the glucose-stimulated incorporation of calcium into the secretory granules is mediated by transport against a concentration gradient into the granule sac.
EFFECTS OF PROLONGED INFUSIONS OF POTASSIUM CHLORIDE, ADRENOCORTICOTROPHIN OR ANGIOTENSIN II UPON SERUM ALDOSTERONE CONCENTRATION AND THE CONVERSION OF CORTICOSTERONE TO ALDOSTERONE IN RATS
Authors: Komor Jan , Müller Jürg
Published: December 2008

The temporal relation between alterations in serum aldosterone and in the conversion of labelled corticosterone to aldosterone by incubated adrenal tissue was studied in conscious rats receiving long-term infusions of KCl, ACTH or angiotensin II. When potassium-deficient rats were given KCl, a marked increase in serum aldosterone was observed only after 12 h, i.e. at a time when the conversion of corticosterone to aldosterone had become normal. After 24 h of ACTH infusion into sodiumand potassium-replete rats the serum aldosterone was markedly elevated, whereas the conversion of corticosterone to aldosterone was significantly decreased. After 48 h of continued ACTH infusion the serum aldosterone returned to normal and there was a further decrease in the conversion rate. A 24-h angiotensin II infusion into sodium- and potassium-replete rats induced significant increases in both the serum aldosterone and the conversion. After 48 h of continued angiotensin infusion the serum aldosterone returned to normal while the conversion and the blood pressure remained elevated. These results indicate that the activity of the enzymes involved in the final steps of aldosterone biosynthesis may become ratelimiting for the secretion of aldosterone during potassium deficiency and during prolonged ACTH treatment. On the other hand, the observed transiency of aldosterone stimulation by exogenous angiotensin II was not due to a suppression of the final steps of aldosterone biosynthesis and remains unexplained.
HORMONE BLOOD LEVELS AND THEIR INTER-RELATIONSHIPS IN NORMAL MEN AND MEN WITH BENIGN PROSTATIC HYPERPLASIA (BPH)
Authors: Bartsch W. , Becker H. , Pinkenburg F.-A. , Krieg M.
Published: December 2008

In 128 non-hospitalized men (age range 36–65 years) rectal palpation revealed in 54 cases an enlargement of the prostate (group II), which was very distinct in 20 cases (group III). The measurement of testosterone (T), 5α-dihydrotestosterone (DHT), 5α-androstane-3α,17β-diol (3α-diol) oestradiol (Oe2), sex-hormone-binding-globulin binding capacity (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (Prl) in the blood of normal men (group I) and those with BPH (group II or III) demonstrated no significant differences between the three groups when respective age ranges were compared. A significant increase of FSH and decrease of 3α-diol with age was seen in the normal group (I), which was similar but less pronounced in BPH (groups II and III). A distinct increase of DHT with age was found in BPH (group II), which was not so dominant in normal men (group I). From these data it is concluded that the conversion of DHT to 3α-diol might be reduced in older males independent from the occurrence of BPH and that the hyperplastic prostate possibly secretes significant amounts of DHT into the circulation. These results are discussed with respect to their possible role in the pathogenesis of BPH.
THE PLASMA FSH AND LH RESPONSE TO SYNTHETIC LH-RH IN NORMAL PRE-PUBERTAL AND EARLY PUBERTAL GIRLS – A RE-EVALUATION
Authors: Dickerman Zvi , Prager-Lewin Ruth , Laron Zvi
Published: December 2008

A standard LH-RH test (50 μg/m2) given iv was carried out in 65 normal girls, 42 of them pre-pubertal aged from 47/12 to 11 years and 23 in the early stage of puberty, aged from 9 to 129/12 years.

The results indicate that in pre-pubertal girls the basal levels of the plasma gonadotrophins remain steady (LH 0.6 ± 0.1 mIU/ml; FSH 0.8 ± 0.1 mIU/ml, m ± sd) and that there is a small but significant response of LH to LH-RH (1.6 ± 0.2 mIU/ml). During this period the FSH response to LH-RH is very marked (8.0 ± 1.0 mIU/ml) with a gradual, significant decrease seen towards the onset of puberty (6.5 ± 0.9 mIU/ml, P < 0.001). These results support earlier reports that the LH-RH test is a useful tool to evaluate the secretion of pituitary LH and FSH in early childhood.
THE FUNCTIONAL STATE OF THE HYPOTHALAMO-PITUITARY AXIS AFTER HIGH-DOSE OESTROGEN THERAPY IN EXCESSIVELY TALL GIRLS
Authors: Hanker J. P. , Schellong G. , Schneider H. P. G.
Published: December 2008

Sixteen excessively tall girls were treated with 0.3 mg of ethinyloestradiol daily and 10 mg of norethisterone for 5 days every 3 weeks for 7–26 months. The reduction of adult height varied from 0–12.3 cm, depending on the bone age (115/12–148/12) before treatment. The more advanced the bone age was the less final adult height was reduced.

The functional state of the hypothalamo-pituitary axis was assessed by standardized LH-RH testing immediately after termination of therapy as well as 1, 4, 8 and 12 weeks thereafter. Basal levels of oestradiol and prolactin were recorded before each test. Absent LH-responses to LH-RH were observed in all girls when therapy was stopped. Four to eight weeks later the LH responses had normalized in 13 girls and 12 weeks after therapy normal LH responses were found in 14 girls.

Mean basal oestradiol levels were low (20 ± 9 pg/ml) (X̄ ± sd) at the end of therapy but increased significantly (P < 0.0025) to levels similar to different stages of the menstrual cycle after 4 weeks. In contrast mean basal prolactin levels were elevated (21±9 ng/ml) (X̄ ± sd) when therapy was stopped. Within one week a significant (P < 0.01) decrease to values averaging 13 ± 4 ng/ml (sd) was seen. A further but only moderate decline occurred until the 12th week after therapy. The decrease of prolactin paralleled to same extend the increase of endogenous oestradiol. All girls experienced spontaneous menstrual bleedings within 3 to 22 weeks after termination of therapy. In all cases but one menses have been regular since.

The data presented suggest that no major functional disturbance of the hypothalamo-pituitary axis has to be expected after long-term steroid treatment in excessively tall girls.
LUTEINIZING HORMONE LEVELS DURING THE MENSTRUAL CYCLE OF THE BABOON (PAPIO HAMADRYAS)
Authors: Goncharov N. , Antonichev A. V. , Gorluschkin V. M. , Chachundocova L. , Robertson D. M. , Diczfalusy E.
Published: December 2008

The peripheral plasma levels of luteinizing hormone (LH) as measured by an in vitro bioassay method were determined in daily plasma samples collected throughout one menstrual cycle in 8 normally menstruating baboons (Papio hamadryas). In addition LH was measured in plasma at three hourly intervals throughout the day in the follicular, peri-ovulatory and luteal phases of the cycle in 7, 3 and 6 animals respectively. The plasma levels of progesterone and oestradiol were also determined in the same samples throughout the menstrual cycle and during the period of the midcycle LH surge.

The circulating LH profile measured throughout the cycle was characterized by a sharp mid-cycle surge (completed within one day) which was followed by a series of LH surges of varying intensity during the luteal phase of the cycle. The initial surge was considered to be pre-ovulatory as indicated by its relationship to the peak of plasma oestradiol and to the first significant increase in the levels of plasma progesterone above values found earlier in the follicular phase.

A circadian rhythm of LH was observed during the luteal phase of the cycle; a 3 fold rise in LH was noted during the hours 15.00 to 24.00. No differences were observed throughout the day in the follicular phase of the cycle.

The LH profile in three animals studied during the mid-cycle LH surge showed pronounced circadian changes with a major peak at 24.00 h. Plasma progesterone levels during this period rose sharply to values normally found in the mid-luteal phase of the cycle.

A comparison of plasma levels of biologically active LH during the menstrual cycle of the baboon with those found in normally menstruating women reveals that in the baboon the LH peak is of much shorter duration and the levels in the follicular and peri-menstrual phases are significantly lower than in the human.
INVESTIGATION OF BONE AND MINERAL METABOLISM IN HYPERTHYROIDISM BEFORE AND AFTER TREATMENT USING CALCITONIN, 47Ca AND BALANCE STUDIES
Authors: Hendriks J. Th. A. M. , Smeenk D.
Published: December 2008

Seventeen normocalcaemic patients with severe hyperthyroidism were examined before therapy was initiated; 9 were re-examined about 1 year later. Studies with 47Ca under balance conditions and with calcitonin demonstrated a high rate of bone resorption in untreated patients. As a result of the increased bone turnover, the reaction to 6 MRC units of porcine calcitonin iv was more marked in the untreated than in the treated patients or the control group. In contrast to the normal diurnal pattern for PO4, it was found that during fasting the plasma PO4 level increases in the morning in patients with hyperthyroidism. This increase which was not suppressed by the administered dose of calcitonin developed in spite of an elevated urinary PO4 excretion.

After treatment, the serum Ca concentration as well as the urinary and faecal Ca excretion was decreased. The Ca balance improved; the rapidlyexchangeable Ca pool returned to normal. The slowly-exchangeable and the total Ca pools, however, remained enlarged. The rate of bone resorption normalized. The accretion rate on the other hand remained elevated. This is attributed to continued enhancement of bone formation to compensate for the previous loss of bony tissue.