bluuebunny/crossref_metadata_2025 huggingface dataset:
CHANGES IN THE PLASMA LEVELS OF ANDROSTENEDIONE, DEHYDROEPIANDROSTERONE AND CORTISOL AFTER STIMULATION WITH ACTH AND hCG AND SUPPRESSION WITH DEXAMETHASONE DURING MALE PUBERTY
Authors: Herrera-Justiniano E. , Galvez M. D. , Aznar A. M. , Gomez S. M. M. , Sendon P. A. , Zurita A. R. , Malagon C. M. , Aznar R. A.
Published: December 2008

Cortisol, androstenedione (Δ4) and dehydroepiandrosterone (DHEA), were evaluated by RIA in a group of 34 adolescent boys, grouped according to genital size. Basal blood samples were taken and 2 mg of dexamethasone administered (12 p.m.). Further plasma samples were taken at 9 a. m. and 250 μg of ACTH injected. Additional samples were drawn after 60 and 120 min. After a lapse of two days 5000 IU of hCG was administered every day for four days and blood samples were taken after the second and fourth injection.

After stimulation with ACTH and suppression with dexamethasone the levels of cortisol were higher and lower, respectively, (P < 0.001) than the basal values. No statistical differences were obtained after the administration of hCG. The levels of Δ4 and DHEA clearly decreased after the administration of dexamethasone and markedly increased after stimulation with ACTH. However, after administration of hCG the levels of both steroids rose but those of the latter did not increase as steeply as those of the former.

With regard to the degree of response of the three steroids in relation to the pubertal stages we noted that cortisol showed a steady response at all stages, while Δ4 and DHEA in contrast, showed a more marked response at stages IV and V than at stages I and II.

These results indicate the primary role that the adrenal glands and the testes play in the rise of levels of DHEA and Δ4 during pubertal development.
EFFECT OF SPIRONOLACTONE AND ITS MAIN METABOLITE CANRENONE ON THE RENIN-ANGIOTENSIN-ALDOSTERONE-SYSTEM DURING LONG-TERM TREATMENT IN RATS
Authors: Erbler Hans C.
Published: December 2008

Spironolactone (SPIR) and its main metabolite canrenone (CAN) were given orally in two different doses to male rats for 6 weeks. Changes in the renin-angiotensin-aldosterone-system (RAAS) served as indicators for alterations in the electrolyte and water balance and thus for the pharmacological activity of the spirolactones studied.

SPIR treatment activated the RAAS dependent on the dose and over the entire period of investigation. In contrast, a comparable activation of the RAAS by CAN was only observed during the first week of treatment. Subsequently the CAN-induced increase in plasma renin activity, plasma aldosterone concentration and urinary aldosterone excretion continuously dropped, indicating a progressive loss in the anti-mineralocorticoid activity of CAN. Plasma sodium and potassium concentrations were significantly changed by SPIR only.

From the results it is concluded that during chronic treatment in the rat the aldosterone-antagonistic effect of SPIR can only be attributed for a limited period to its main metabolite CAN. In long-term treatment CAN is obviously subject to an accelerated metabolism and thus contributes only to a limited extent to the anti-mineralocorticoid effects of SPIR. In the rat the major part of the aldosterone-antagonistic effect of SPIR is possibly maintained during long-term treatment by sulphur-containing SPIR metabolites which arise from SPIR by metabolic degradation of the thioacetyl group.
PROGESTERONE AND 20α-HYDROXYSTEROID-DEHYDROGENASE REGULATION IN THE CORPUS LUTEUM OF THE PREGNANT RAT
Authors: Loewit K. , Zambelis N.
Published: December 2008

Female Wistar rats were mated and passively immunized against bovine luteinizing hormone (bLH) between days 7–12 of gestation. In a first series of experiments the effect of simultaneous progesterone treatment on the histochemically detectable activity of 20α-hydroxysteroiddehydrogenase (20α-OHSD) in the corpora lutea of pregnancy was evaluated. In other experiments the exact time course was established between the first histologically demonstrable signs of termination of pregnancy and the appearance of 20α-OHSD activity in corpora lutea of pregnancy.

It was found that progesterone substitution not only prevented the deleterious effects of the anti-bLH-serum on gestation but also the re-appearance of 20α-OHSD activity in the corpora lutea of pregnancy up to day 12 of pregnancy. Moreover in animals injected with anti-bLH-serum from day 7 on and sacrificed on days 8–2, signs of foetal destruction clearly preceded the pathological re-appearance of 20α-OHSD activity by 2–3 days. These results support previous findings on a direct or indirect role of progesterone in the complex regulation of 20α-OHSD activity. Possible mechanisms of action are discussed.
IN VITRO C-20, 22 DESMOLASE REGULATION OF PREGNENOLONE SUPPLY IN FIRST TRIMESTER HUMAN PLACENTA
Authors: Gunasegaram R. , Peh K. L. , Chew P. C. T. , Karim S. M. M. , Ratnam S. S.
Published: December 2008

Homogenates of first trimester human placentae were incubated with [26-14C]cholesterol. Using reverse-isotope dilution analysis [14C]isocaproic acid was isolated and characterized. A progressive increase in [14C]isocaproic acid formation with increasing gestation suggestive of a regulatory mechanism at the C-20,22 desmolase site in the supply of placental pregnenolone was noted.
DUAL ACTION OF ADRENERGIC SYSTEM ON THE REGULATION OF THYROTROPHIN SECRETION IN THE MALE RAT
Authors: Männistö Pekka , Ranta Tapio , Tuomisto Jouko
Published: December 2008

The effect of graded doses of drugs modifying adrenergic activity on basal and cold-stimulated TSH secretion was studied in male rats, ±-Methyl-p-tyrosine (±MPT) (16 h before 30 min cold-exposure), phenoxybenzamine (1 h), Ca-fusarate (1 h) and diethyldithiocarbamate (DDC) (1 and 18 h) dose-dependently depressed the cold-stimulated TSH secretion. The effect of reserpine (24 h) was not significant. Clonidine (1 h), dihydroxyphenylserine (DOPS) (1 h), noradrenaline (NA) (1 h), and l-Dopa (1 h) were also effective in decreasing serum TSH levels, but dopamine (DA) (ad 2 mg/kg, 1 h) had no effect. Basal TSH levels were also decreased by various doses of clonidine, DOPS and NA, given ip 1 h before sacrifice. Clonidine (1 mg/kg), NA (1 mg/kg), DA (2 mg/kg), ±MPT (300 mg/kg), phenoxybenzamine (2 or 20 mg/kg), Ca-fusarate (50 mg/kg) or l-Dopa (200 mg/kg) did not modify the TRH-induced TSH response. These results cannot be explained by assuming only a stimulatory function for the adrenergic system on the secretion of TSH in the rat. The site of the possible inhibitory function of noradrenaline in the control of TSH cannot be deduced from these results, but various possibilities are discussed.
DEVELOPMENT OF POLYPLOIDY IN B-CELLS OF NORMAL AND DIABETIC MICE
Authors: Pohl M. N. , Swartz F. J.
Published: December 2008

This study was designed to clarify the relationship between pancreatic B-cell polyploidization and the progress of the diabetic syndrome in genetically diabetic (C57BL/Ks-db/db) and normal control mice (C57BL/KsJ) of matched age groups. Nuclear volume was confirmed to be a proper index of the polyploid class of the B-cell by correlation with Feulgen-DNA content as measured by microdensitometry. Nuclei of B-cells, identified by aldehyde fuchsin positive cytoplasmic granules, were traced by camera lucida and their volumes determined by semiautomatic particle size analysis. Six age groups were studied: 4.5, 7, 9.5, 12, 14.5 and 17 weeks. The major conclusions are: 1) The percentage of tetraploid nuclei in normal mice is consistently between 1.0 and 2.0% from 4.5 to 14.5 weeks of age and increases to approximately 3.0 % at 17 weeks of age; however, further studies are required to determined the significance of this increase; 2) in all age groups studied, percentages of polyploid nuclei are significantly greater in diabetic than in control mice; 3) the percentage of tetraploid nuclei in diabetic animals is elevated 220 % over controls at 4.5 weeks of age, remains constant until 12 weeks (while other parameters such as blood glucose level and body weight continue to rise) and increases significantly between 12 and 14.5 weeks of age. Implications of both the increased polyploidy observed at the onset of disease symptoms, and the dramatic increase occurring during the later stages of the disease, are discussed.
IMMUNOHISTOCHEMICAL LOCALIZATION OF ADRENODOXIN AND ADRENODOXIN REDUCTASE IN BOVINE ADRENAL CORTEX
Authors: Mitani Fumiko , Ishimura Yuzuru , Izumi Shinichi , Watanabe Keiichi
Published: December 2008

The zonal distribution of adrenodoxin and adrenodoxin reductase (EC 1.6.7.1) in the bovine adrenal cortex as well as their intracellular localization has been studied by the direct method of peroxidase-labelled antibody (Fab′ or F(ab′)2 fraction) technique. The results indicated that both proteins localized mainly in zonae fasciculata and reticularis whereas very few were present in the zona glomerulosa. Only parenchymal cells in the adrenal cortex were proved to contain both proteins.

The intracellular localization of both adrenodoxin and the reductase was demonstrated to be exclusively on the inner membrane of mitochondria of these parenchymal cells by immunoelectron microscopy. The validity of the immunocytochemical method employed in this study to determine the fine localization of both proteins in the mitochondria as well as the significance of the zonal distribution in relation to the function of each individual zone is discussed.
EFFECT OF STRESS ON THE PROFILE OF PLASMA STEROIDS IN BABOONS (PAPIO HAMADRYAS)
Authors: Goncharov N. P. , Taranov A. G. , Antonichev A. V. , Gorlushkin V. M. , Aso T. , Cekan S. Z. , Diczfalusy E.
Published: December 2008

Adult baboons (5 males and 5 females) were exposed to immobilization stress by being strapped to a table in a horizontal position for 2 h. In females the experiment was performed during both the follicular and luteal phase. Peripheral blood was withdrawn at frequent intervals, the first sample just before immobilization, and the last one 3 days later. A number of steroids were measured in blood plasma samples by radioimmunoassay (17-hydroxypregnenolone, 17-hydroxyprogesterone, pregnenolone, testosterone, dihydrotestosterone, progesterone, 20α-dihydroprogesterone, oestrone, oestradiol) or competitive protein binding (cortisol) techniques.

The cortisol levels exhibited a marked increase in both sexes. This increase was observed already during the immobilization and lasted for approximately 24 h. A similar, even more pronounced increase was seen in 17-hydroxypregnenolone, 17-hydroxyprogesterone and pregnenolone levels. A marked, long-lasting (72 h) decrease of testosterone and dihydrotestosterone levels was a consistent finding in male baboons. This was not observed in the females which, on the other hand, exhibited a marked decrease (duration 48 h) of progesterone and 20α-dihydroprogesterone levels during the luteal phase, and a significant decrease (duration > 24 h) of oestradiol and oestrone concentrations during the follicular phase.

It is concluded that stress has a marked inhibitory action on gonadal function both in male and female baboons. In females the inhibition of steroidogenetic function is exerted both on the ovarian follicles and on the corpus luteum.
SHORT-TERM REGULATION OF LH AND FSH SECRETION IN CYCLIC WOMEN
Authors: Römmler A. , Viebahn C. , Schwartz U. , Hammerstein J.
Published: December 2008

The effects of two consecutive LH-RH injections at 120 min intervals with either a varying first or second LH-RH dose on pituitary gonadotrophin response were investigated in 15 eugonadal women to study pituitary secretory processes. Each volunteer underwent a total of 4 LH-RH double stimulation tests. In group I (n = 8) the first LH-RH dose of each of the 4 tests was fixed at 25 μg, whereas the second LH-RH dose consisted of either 6, 25, 100 or 400 μg. In group II (n= 7) the first LH-RH dose varied between 6 and 400 μg, while the second LH-RH dose was kept constant at 25 μg. Serum gonadotrophin and serum ovarian steroid levels were determined by radioimmunoassay before and after LH-RH administration. The volunteers in both groups served as their own controls.

A linear log-dose response relationship was found between the various doses of LH-RH injected and the corresponding LH and FSH elevations elicited. However, the dose of the first LH-RH injection also significantly influenced the gonadotrophin reaction after the second LH-RH injection in a linear log-dose response relationship. Serum levels of oestradiol, 17-hydroxyprogesterone and progesterone significantly increased in response to the elevated serum gonadotrophin levels after LH-RH stimulation during the 4 h test period, but the rise did not correlate to the LH-RH dose used.

The results indicate that LH-releasing hormone stimulates not only the release, but also the synthesis of LH and FSH in a dose-related manner. These findings are consistent with our previously reported concept that the magnitude of LH and FSH response to the first LH-RH injection reflects the "storage capacity", while the increase observed after the second LH-RH injection represents the "synthesis capacity" of the gonadotrophs.
NON-SUPPRESSIBLE INSULIN-LIKE ACTIVITY IN LARON'S SYNDROME
Authors: Kastrup Knud W. , Zapf Jürgen
Published: December 2008

Severe growth retardation is found in patients with high levels of growth hormone and low sulphation factor activity or somatomedin. Also nonsuppressible insulin-like activity (NSILA-s) has been found to be very low in a patient with this condition as measured by bioassay, protein binding assay and radioimmunoassay and to be below activities found in hypopituitary patients. Partially purified NSILA-s restored the ability of serum to increase sulphation activity although full restitution may still depend on other factors. These findings support the hypothesis that NSILA-s belongs to the family of somatomedin and thus is involved in promoting growth, and that low activity of these growth factors is a primary cause of the growth retardation found in these patients.
SEX AND AGE CORRELATED REFERENCE VALUES OF SERUM THYROGLOBULIN MEASURED BY A MODIFIED RADIOIMMUNOASSAY
Authors: Feldt-Rasmussen Ulla , Petersen Per Hyltoft , Date John
Published: December 2008

The aim of the present investigation was to describe variations in serum thyroglobulin in relation to sex and age in a group of normal persons. The method used was a modified double antibody radioimmunoassay characterized by pre-incubation at 37°C of standard or sample with antiserum, resulting in a reduced total incubation time. Both sensitivity and precision were comparable to other published methods.

Of the 152 blood-donors initially investigated, 7 were excluded due to the presence of antithyroglobulin antibodies as evidenced by a radioassay. Both sexes were equally represented with an even distribution of ages from 20-65 years.

Increased serum thyroglobulin with increasing age was demonstrated, the correlation being significant in women (Kendall's τ, P < 0.001). Detectable concentrations of serum thyroglobulin (above 1.7 μg/l) were found in 94 %. Based on the logarithmic transformation, the upper reference limits were determined for men ≦ 40 years: 36 μg/l, > 40 years: 44 μg/l (difference between groups not significant, P > 0.05), and for women ≦ 40 years: 30 μg/l, > 40 years: 60 μg/l (significant difference, P < 0.005).
ATP-INDUCED RELEASE OF VASOPRESSIN FROM ISOLATED BOVINE NEUROHYPOPHYSEAL SECRETORY GRANULES. DEPENDENCY ON CHLORIDE AND EFFECTS OF ANALOGUES OF ATP
Authors: Overgaard Karsten , Torp-Pedersen Christian , Thorn Niels A.
Published: December 2008

Secretory granules isolated from bovine neurohypophyses released vasopressin in the presence of a buffered medium containing ATP, Mg2+ and KCl.

Substitution of K+ in the medium with Na+ or choline did not affect the release. Substitution of Cl− with either sucrose, sulphate or acetate strongly reduced the release.

Analogues of ATP, substituted at the β-γ anhydride bond with methylene or imido groups caused a smaller release which was not related to a very small breakdown of analogues that occurred.

It is suggested that at least part of the ATP induced release is due to a physicochemical action.
THE EFFECT OF FENFLURAMINE ON OBESE, MATURITY-ONSET DIABETIC PATIENTS
Authors: Wales John K.
Published: December 2008

In 38 obese maturity-onset diabetic patients the effect of fenfluramine therapy on carbohydrate tolerance was compared to placebo therapy in a double blind trial. Fenfluramine therapy did not affect weight loss, or fasting glucose levels but produced a slight but significant improvement in glucose tolerance. This improvement was not correlated with any change in body weight or insulin secretion.
THE EFFECT OF DIFFERENT EXTRACTION PROCEDURES ON TWO DIFFERENT MOLECULAR WEIGHT SPECIES OF SERUM NSILA AND ON THE CARRIER PROTEIN OF SMALL MOLECULAR WEIGHT NSILA (NSILA-S)
Authors: Kaufmann U. , Zapf J. , Froesch E. R.
Published: December 2008

The influence of Dowex-50 adsorption chromatography on the recovery of two different forms of serum NSILA, large and small mol. wt. NSILA, and on the recovery of the binding protein of the small mol. wt. form was studied and compared with another extraction procedure, gel filtration on Sephadex G-50 in 1 m acetic acid.

Partially purified NSILA-S is adsorbed to Dowex-50 at pH 6.8. It can be eluted with 20 mm NH4OH and appears unchanged with regard to its biological activity and molecular weight. Adsorption of 125I-labelled NSILA-S to Dowex-50 does not change its binding characteristics to serum.

When serum is chromatographed on Sephadex G-50 in 1 m acetic acid, NSILA is obtained in a large and in a small molecular weight form (NSILA-S). After recombination of the small molecular weight NSILA fraction with the "stripped" serum fraction, which contains large mol. wt. NSILA and a specific carrier protein for NSILA-S, re-chromatography of this mixture on Sephadex G-50 at neutral pH yields NSILA mostly in the void volume. It adsorbs to Dowex-50. After elution from Dowex, acidic gel filtration on Sephadex G-50 results in an elution pattern which is completely different from that of NSILA-S.

Adsorption of serum to Dowex-50 results in a dramatic decrease of the NSILA-S binding activity.

It is concluded that Dowex-50 adsorption chromatography of serum

inactivates most of the serum NSILA-S binding protein

leads to the loss of acid dissociable small mol. wt. NSILA (NSILA-S). Therefore, Dowex-50 adsorption chromatography is not suitable for the subsequent determination or further purification of NSILA-S from whole serum.
DIURNAL FLUCTATION OF PLASMA CORTISOL LEVELS IN THE GUINEA PIG
Authors: Garris David R.
Published: December 2008

Diurnal changes in the basal levels of plasma cortisol were studied in the female guinea pig. Plasma cortisol levels were determined at 8 bleeding times during the entrained 24 h photoperiod (14 h light/10 h dark: lights on 06.00 h). Plasma cortisol levels remained low during the dark phase of the cycle ranging between 6.4 and 9.0 μg/100 ml. However, at 4 h prior to the onset of the light phase of the photoperiod, a dramatic rise in the plasma cortisol level was measured, which peaked between 04.00 and 08.00 h at 12.3 μg/100 ml. A subsequent decline in plasma cortisol levels was measured throughout the light phase of the cycle, reaching basal levels before the onset of the dark phase. These data indicate that a diurnal fluctation in plasma cortisol occurs in the guinea pig which is very reminiscent of that seen in the human and in contrast with that observed in the rat.
DIFFERENTIAL PROPERTIES OF HUMAN CHORIONIC GONADOTROPHIN AND HUMAN LUTEINIZING HORMONE BINDING TO PLASMA MEMBRANES OF BOVINE CORPORA LUTEA
Authors: Rao Ch. V.
Published: December 2008

Plasma membranes of bovine corpora lutea contain common receptor sites for [125I] human chorionic gonadotrophin (hCG) and [125I] human luteinizing hormone (hLH) to which hLH binds with 4-fold lower affinity than hCG. The presence of additional sites for hLH was indicated by the lack of saturation of [125I]hLH binding as compared to [125I]hCG and lower degree of inhibition of binding by 830 pm of unlabelled hCG, when [125I]-hLH instead of [125I]hCG was used. Differences in [125I]hCG and [125I]-hLH binding were observed by exposing receptors to increasing temperatures and pHs and by pre-treating membranes with dimethyl sulphoxide, Triton X-100, various enzymes and protein reagents. The above differences can only be reconciled by differential responses of common hCG-hLH sites and additional sites for hLH.
RESTORATION OF THE GONADOTROPHIN RESPONSE TO LH-RH AND OESTROGEN ADMINISTRATION IN PATIENTS AFTER MOLAR ABORTION
Authors: Miyake A. , Aono T. , Tanizawa O. , Kurachi H. , Kurachi K.
Published: December 2008

The relation of the hypothalamic-pituitary effect on gonadotrophin secretion and the concentration of serum hCG after molar abortion was investigated. Gonadotrophin release after a bolus injection of LH-RH or conjugated oestrogens was observed in 17 women until 5 months after molar abortion. Little if any response of gonadotrophin was observed at a hCG level of 100 mIU/ml or more, but the response of LH and FSH to LH-RH were restored to normal when the serum hCG level decreased to below 100 mIU/ml. A normal response of LH to conjugated oestrogens was observed at a serum hCG level of 20 mIU/ml or less. These findings suggest that a high level of hCG interferes with pituitary gonadotrophin secretion, that the threshold hCG levels for normal responses of gonadotrophins to LH-RH and oestrogen are 100 and 20 mIU/ml, respectively, and that secretion of gonadotrophins is restored even in the presence of a low hCG level.
INTERACTION OF DAILY INJECTIONS AND SUBCUTANEOUS RESERVOIRS OF MELATONIN ON THE REPRODUCTIVE PHYSIOLOGY OF FEMALE SYRIAN HAMSTERS
Authors: Trakulrungsi C. , Reiter R. J. , Trakulrungsi W. K. , Vaughan M. K. , Waring-Ellis P. J.
Published: December 2008

This study investigated the ability of continuously available melatonin (from sc melatonin-beeswax pellets that were implanted bi-weekly) in overcoming the antigonadotrophic action of single daily melatonin (25 μg) injections given late in the light period to female Syrian hamsters kept in light:dark cycles of 14:10. The melatonin-beeswax pellets contained either 1, 50, 500 μg, 1 or 10 mg melatonin and 25 mg beeswax. Daily melatonin injections into hamsters implanted with beeswax only caused vaginal acyclicity in 60 % of the animals within 6 weeks. After 10 weeks of treatment, uterine weights and pituitary levels of immunoreactive prolactin were still greatly depressed. Beeswax pellets containing either 500 μg, 1 or 10 mg melatonin overcame the inhibitory effects of daily melatonin injections. Thus, the vaginal cycles and pituitary hormone levels of these animals were indistinguishable from those of untreated control animals. Beeswax pellets containing either 1 or 50 μg melatonin were incapable of counteracting the antigonadotrophic effects of daily injections of melatonin. This is the first report that continuously available melatonin can negate the effects of daily injections of melatonin in female hamsters. When measured after 10 weeks, none of the treatment procedures significantly influenced circulating levels of luteinizing hormone or prolactin.
MACROPHAGE-LYMPHOCYTE INTERACTION IN GRAVES' DISEASE AND HASHIMOTO'S THYROIDITIS
Authors: Sugenoya Akira , Silverberg Jay , Trokoudes Krinos , Row Vas V. , Volpé Robert
Published: December 2008

The formation of macrophage-lymphocyte rosettes was studied in lymphocyte cultures from patients with Graves' disease, Hashimoto's thyroiditis, other thyroid diseases and control subjects; the cultures were incubated with normal human thyroid and other non-specific antigens. At the end of incubation, the cell pellets were smeared on slides, stained with Wright's stain and the number of rosettes determined under the microscope. The membrane immunofluorescence technique was employed to identify whether the surrounding lymphocytes were T- or B-lymphocytes. In Graves' disease and Hashimoto's thyroiditis, the mean percentages of rosette formation with crude thyroid antigen were 0.98 ± 0.22 % (mean ± sem), and 1.15 ± 0.25 %, respectively. These values were significantly higher than those of control lymphocytes (0.03 ± 0.02 %). Lymphocytes from other thyroid diseases also gave higher values than controls. Kidney antigen, used as a control antigen, gave negative results in Graves' disease and other thyroid diseases, but in Hashimoto's thyroiditis, the mean percentage was of borderline significance. In the direct immunofluorescent staining study using fluorescein-conjugated goat anti-human Ig determinants, including the Fab fraction of anti-human IgG, it appeared that both B- and T-lymphocytes were involved in the rosettes, although B-lymphocytes were more numerous. These results indicate that in patients with Graves' disease and Hashimoto's thyroiditis, a probable immune reaction with thyroid antigen can be demonstrated by macrophage-lymphocyte rosette formation.
CIRCADIAN RHYTHMS OF PLASMA CORTICOSTERONE BINDING ACTIVITY IN THE RAT AND THE MOUSE
Authors: Ottenweller John E. , Meier Albert H. , Russo Albert C. , Frenzke Marie E.
Published: December 2008

Corticosterone binding activity (CBA) and corticosteroids were measured by competitive protein binding techniques in plasma samples drawn from rats and mice at different times of day. Circadian rhythms of plasma CBA were found in both rats (onset of 14-h daily photoperiod: 0600) and mice (onset of 14-h daily photoperiod: 0700). The plasma CBA rhythm was bimodal in rats with peaks at 1000 and 1800 and unimodal in mice with peak level from 0100 to 0500. Circadian rhythms of plasma corticosteroid concentration with peaks during the late afternoon were confirmed in both rats and mice. The plasma CBA rhythms appear to be related to the circadian rhythms of both locomotor activity and plasma corticosteroid concentration.
GIGANTISM ASSOCIATED WITH A PITUITARY TUMOUR SECRETING GROWTH HORMONE AND PROLACTIN AND CURED BY TRANSSPHENOIDAL HYPOPHYSECTOMY
Authors: Favre Laurent , Rogers Lowell M. , Cobb Cully A. , Rabin David
Published: December 2008

An 18-year old male is reported who presented with a history of a growth spurt over the year preceding his admission. His height was above the 97th percentile, and he had incompletely developed secondary sexual characters. Pituitary evaluation demonstrated a moderately elevated level of growth hormone (hGH) not suppressible by a glucose load and not stimulable by TRH or by l-DOPA. Serum prolactin (PRL) concentration was also increased while gonadotrophin, thyroid and adrenal function were all subnormal. There was clear radiological evidence of a large pituitary tumour with suprasellar extension and transsphenoidal total hypophysectomy was performed. A mixed chromophobe and acidophilic adenoma was found and both growth hormone and prolactin were demonstrable in different cells of the tumour by the immunoperoxidase technique. Post-operatively the patient has hypopituitarism and levels of growth hormone and prolactin have remained low or undetectable after 6 months. Thus early diagnosis and surgical treatment of gigantism of this mixed hGH-PRL secreting pituitary tumour was associated with a cure, which contrasts with the unfavourable outcome of many of the patients previously reported.
CHARACTERIZATION OF SPECIFIC ANTISERA TO NATIVE HUMAN LUTEINIZING HORMONE
Authors: Jeppsson Sten , Larsson Ingvar , Thorell Jan I.
Published: December 2008

Antisera against highly purified native hLH (10 000 IU/mg = 0.5 mg hLH/mg protein) were raised in 4 rabbits. The antisera were invariably of high titre and high avidity. They were purified by affinity chromatography on a column with hCG-Sepharose 4 B. Before and after adsorption the antisera were tested in a double antibody radioimmunoassay.

Before adsorption hCG cross-reacted in all antisera, but in none were the inhibition curves identical. No such cross-reaction remained after the affinity chromatography. These purified antisera made it possible to develop highly specific and sensitive assays for measuring native hLH.

We conclude from studies of the effect of native glycoprotein hormones and their subunits that there are probably differences in the antigenic sites of the complete hLH molecule and in the isolated β-subunit of hLH. The investigation also indicates that even highly purified preparations of hTSH may be contaminated with hLH and that the preparations of hLH-subunits may contain a certain amount of the native hormone.
PLASMA CORTISOL PROFILES IN CUSHING'S SYNDROME
Authors: Yoshida Koichiro , Satowa Hiroshi , Sato Akio , Ichikawa Yoichi , Kream Jacob , Levin Joseph , Zumoff Barnett , Hellman Leon , Fukushima David K.
Published: December 2008

Plasma cortisol profiles were studied by the frequent sampling method in 5 patients with Cushing's disease (CD), 7 patients with Cushing's syndrome due to adrenocortical adenoma (AA), and one patient with bronchogenic carcinoma. Plasma ACTH was measured by radioimmunoassay at 10 min intervals in 2 of the subjects. In CD, there was distinct episodic secretion of cortisol and ACTH; the coefficients of variation about the mean plasma cortisol concentration ranged from 24 to 27 %; plasma ACTH ranged from zero to 455 pg/ml with a mean of 94 pg/ml. In AA, the tumour secreted cortisol at a constant rate with little fluctuation; the coefficients of variation of plasma cortisol concentration ranged from 8 to 14%; plasma concentrations of ACTH were always near zero. In the patient with bronchogenic carcinoma, the coefficient of variation of cortisol was 14 %. These results were apparent even in profiles of plasma cortisol concentrations measured over only a 6 h period. It is concluded that characteristics of plasma cortisol and ACTH secretory patterns are helpful in differentiating Cushing's syndrome of differing aetiology.
MEASUREMENT OF CIRCULATING 1,25-DIHYDROXYVITAMIN D IN MAN. CHANGES IN SERUM CONCENTRATIONS DURING TREATMENT WITH 1α-HYDROXYCHOLECALCIFEROL
Authors: Lund Bjarne , Lund Birger , Sorensen Ole H.
Published: December 2008

A sensitive assay is described for measurement of circulating 1,25-dihydroxyvitamin D (1,25-(OH)2D) using rachitic chick intestinal cytosol binding protein. The metabolite was extracted from serum by diethyl ether and chromotographed on a Sephadex LH-20 column followed by high-pressure liquid chromatography. The concentration of 1,25-(OH)2D was then measured by a competitive protein-binding assay. The binding capacity of the protein was unchanged for 4 months. The inter- and intra-assay variations were both 11 %. The standard curve was useful at serum concentrations ranging from 14 to 395 pmol/l (6 to 165 pg/ml). The normal mean concentration was 79.6 ± 36.8 pmol/l (33.1 ± 15.3 pg/ml). The serum 1,25-(OH)2D was studied in elderly subjects following administration of 1α-hydroxycholecalciferol (1α-OHD3) at different doses. Large variations occurred indicating individual rates of metabolism of 1,25-(OH)2D.
THE EFFECT OF METOCLOPRAMIDE, TRH AND L-DOPA ON PROLACTIN SECRETION IN PITUITARY ADENOMA AND IN "FUNCTIONAL" GALACTORRHOEA SYNDROME
Authors: Jeske W.
Published: December 2008

The degree of autonomy in prolactin secreting pituitary adenomas and also prolactin secretory reserve in cases with suspected functional galactorrhoea syndrome was evaluated with the use of metoclopramide, TRH and L-DOPA.

It was found that in patients with pituitary adenoma the basal prolactin (PRL) level often exceeded 150 μg/l and the response to stimulation with TRH and/or metoclopramide was markedly diminished or even nonexistent, while the response to L-DOPA was usually retained. In patients with galactorrhoea and/or amenorrhoea, with normal skull X-ray the basal PRL level was either normal or moderately raised but the response to stimulation was various; mostly it was excessive, it was sometimes normal, but in some other cases it was markedly diminished as in patients with adenoma.

In the author's opinion the so-called "functional disorder" of prolactin secretion is mainly hyperresponsiveness to stimulation, whereas the basal PRL level in those cases is usually normal or only intermittently raised. In the cases with a moderate hyperprolactinaemia, especially if it appears to be constant, and the response to stimulation is diminished or none at all, we suspect a pituitary microadenoma. Finally, there are rare cases of galactorrhoea with normal basal PRL and normal response to stimulation, in which the sensitivity of the mammary PRL receptor is probably increased.

We suggest therefore that the above mentioned PRL stimulation tests may help in distinguishing between tumoural and functional hyperprolactinaemia.
RECEPTORS FOR GONADOTROPHIN AND PROSTAGLANDIN F2α IN BOVINE CORPORA LUTEA OF EARLY, MID AND LATE LUTEAL PHASE
Authors: Rao Ch. V. , Estergreen V. L. , Carman F. R. , Moss G. E.
Published: December 2008

A total of 15 corpora lutea representing early (day 3), mid (day 13) and late luteal phase (days 20 and 21–24) were obtained by ovariectomy on cycling cows. The luteal weights and peripheral plasma progesterone levels just prior to ovariectomy, were consistent with the above luteal phases. The specific binding of [125I]human chorionic gonadotrophin to membranes prepared from corpora lutea was significantly higher (P < 0.01) for days 13 and 20 than for days 3 and 21–24. The binding in day 21–24 corpora lutea was higher (P < 0.01) than day 3. Although there was no difference either in number or affinity (apparent dissociation constant (Kd) = 0.04 nm) of gonadotrophin receptors in days 13 and 20 corpora lutea, only in the former did the binding correlate well with plasma progesterone levels. The specific binding of [3H]prostaglandin (PG)F2α to the membranes of these same corpora lutea showed a progressive increase (P < 0.01) from day 3, reached the highest value at a time when corpora lutea were actively regressing (day 20) and then declined (P < 0.01) by day 21–24. Although a considerable number of PGF2α receptors existed at day 13, the affinity of these same receptors was 203 times lower (Kd = 3458 nm) than the affinity of receptors in day 20 corpora lutea (Kd = 17 nm). In summary, the above results show that gonadotrophin receptors correlate with luteotrophic, whereas PGF2α receptors correlate with luteolytic phases in bovine corpora lutea.
THE EFFECTS OF LOW DOSES OF CYPROTERONE ACETATE ON SOME FUNCTIONS OF THE REPRODUCTIVE SYSTEM IN NORMAL MEN
Authors: Føgh Marie , Corker Charles S. , Hunter William M. , McLean Helen , Philip John , Schou Geert , Shakkebæk Niels E.
Published: December 2008

One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly (0.001 < P < 0.05). Sperm penetration assessed by the Kremer test did not show any decrease during treatment. Serum levels of testosterone and FSH decreased, but those of LH remained unchanged during treatment. Two pregnancies occurred after 1¾ and 5½ months of CA-treatment. The serum-CA concentration in these 2 volonteers did not differ from that of the remainder.

Three subjects who began the study were withdrawn because of depressive mood changes (2) and weakness combined with dizziness (1). Data from these subjects were not included.

The results indicate that daily doses of 5 mg and 10 mg of cyproterone acetate are not effective as a male contraceptive.
TESTOSTERONE DECREASE AND OESTROGEN INCREASE IN MALE PATIENTS WITH OBESITY
Authors: Kley H. K. , Solbach H. G. , McKinnan J. C. , Krüskemper H. L.
Published: December 2008

The concentration of sex hormones and their binding in the plasma were measured in male patients (20–40 years old), who weighed 140–170 % (I), 170–200 % (II) and > 200 % (III) of their ideal weight. Correlated to body weight, there is a reduction in the total concentration of testosterone, which, in the very obese patients, amounts to 41 % (in group I: 85 % in group II: 68 % P < 0.001) of that found in an age-matched healthy control group of subjects of "normal" body weight (90–115 % of the ideal body weight; n: 20). Androstenedione values show only a trend downwards (from 0.94 to 0.72 ng/ml plasma), while the oestrogen values increase significantly; oestrone increases by a factor of 1.09 (I), 1.43 (II; P < 0.001) and 1.69 (III; P < 0.001) and oestradiol by 1.13, 1.43 P < 0.001) and 1.76 (P < 0.001), respectively. Despite the fall in testosterone there are no clinical signs of hypogonadism, as SHBG (from 5.1 ± 0.8 in the controls to 2.4 ± 0.6 ×10−8 Mol/l in the very obese patients of group III) and the protein-bound fraction of testosterone also decrease. As a result the concentration of free testosterone remains constant (120 pg/ml), except in the very obese (93 pg/ml). Because of the different affinity of the binding proteins for testosterone and oestradiol the ratio of free oestradiol: free testosterone shifts less strongly in favour of the feminizing hormone (11.1 × 10−3 in group III as compared to 4.1 × 10−3 in the controls), than is suggested by the total hormone concentrations. A disturbance in the gonadal function of the pituitary gland or the testes is not present, since the concentration of LH is normal and the testicular response to HCG in very obese patients adequate (increase of testosterone by a factor of 3.11 as compared to 2.23 in the controls). The cause of the decrease in testosterone and SHBG is unknown, while the increase of plasma oestrogens is likely to be due to the increased conversion of androgens to oestrogens in the adipose tissue, which clearly plays an important role for plasma concentrations of sex hormones in obese patients.
SERUM GASTRIN AND SERUM CALCITONIN IN PATIENTS WITH CHRONIC RENAL FAILURE
Authors: Christensen C. K. , Nielsen H. E. , Kamstrup O. , Olsen K. J. , Brandsborg M. , Brandsborg O.
Published: December 2008

The interrelationship between serum gastrin and serum calcitonin concentrations was studied in 73 patients with chronic renal failure. In both haemodialyzed and non-dialyzed patients increased serum concentrations of these hormones were found compared with normal controls. In non-dialyzed patients with creatinine clearance above 10 ml/min a highly significant correlation between serum gastrin and creatinine clearance was found, whereas no correlation was found in patients with creatinine clearance below 10 ml/min. Between serum gastrin and serum calcitonin, a significant positive correlation was found in non-dialyzed patients. whereas no correlation could be demonstrated in haemodialyzed patients. These findings may be explained by a relationship between the two hormones or be secondary to a decreased elimination due to the reduced renal function.
GONADOTROPHIN-RELEASE UPON INTRAVENOUS ADMINISTRATION OF A LONG-ACTING ANALOGUE OF LUTEINIZING HORMONE-RELEASING HORMONE IN FEMALES WITH INCREASED PLASMA-ANDROGENS
Authors: Vierhapper H. , Waldhäusl W. , Nowotny P.
Published: December 2008

D-Ser-(TBU)6-EA10-LH-RH, an analogue of luteinizing hormone-releasing hormone (LH-RH) with prolonged action evokes in normal male and female subjects a qualitatively different secretory pattern of LH, as peak levels are reached between 30 and 60 min in males and between 120 and 240 min in females. Females with increased production of adrenal androgens due to congenital adrenal hyperplasia (off substitution therapy; N = 8), idiopathic hirsutism (N = 1) and adrenocortical carcinoma (N = 2) present upon the administration of the LH-RH-analogue with a secretory pattern of LH and FSH which is qualitatively identical with that of normal female subjects, whereas the response of LH in these patients differs from that seen in normal males. Pre-treatment with dexamethasone did not induce any qualitative changes in the secretory response of LH and FSH upon the LH-RH-analogue in patients with increased endogenous production of adrenal androgens. A larger pool and/or a more pronounced de novosynthesis of LH, which apparently is not altered by increased levels of adrenal androgens, may be the cause of the more pronounced and prolonged increase of LH in female subjects following the administration of the LH-RH-analogue.
EFFECTS OF ACTIVE AND PASSIVE IMMUNIZATION WITH LH-RH ON GONADOTROPHIN SECRETION AND REPRODUCTIVE FUNCTION IN FEMALE RATS
Authors: Kawakami Masazumi , Higuchi Takashi
Published: December 2008

In order to get information about the physiological role played by LH-RH in the regulation of tonic and phasic secretion of gonadotrophins, and about the existence of FSH-RF distinct from LH-RH, we attempted to neutralize endogenous LH-RH by passive and active immunization with LH-RH in female rats.

Anti-LH-RH serum prevented pre-ovulatory gonadotrophin surges at prooestrus and ovulation, and it suppressed gonadotrophin increase induced by oestradiol benzoate or progesterone in ovariectomized rats.

Elevated serum gonadotrophin concentrations in long-term ovariectomized rats were lowered by anti-LH-RH serum injection. The decrease in FSH levels was lesser than that in LH levels. Serum FSH rose without significant changes in serum LH level for 6 h after ovariectomy on pro-oestrus or dioestrus. The post-ovariectomy rise of FSH was not suppressed by the anti-LH-RH serum which was enough to inhibit serum LH to undetectable levels.

Active immunization with LH-RH resulted in decreasing LH levels but failed to alter FSH levels in both serum and pituitary. Seven out of 10 rats immunized with LH-RH became constantly di-oestrous. The weights of anterior pituitary, ovary and uterus of the LH-RH immunized rats were significantly smaller than those of BSA immunized controls. Ovaries of LH-RH immunized rats contained few fresh corpora lutea.

These results indicate that LH-RH plays a significant role in the control of both phasic and tonic secretion of LH and FSH. The existence of FSH-RF distinct from LH-RH or mechanism which specially controls the basal FSH secretion is indicated.
EFFECT OF ENDOGENOUS THYROID STIMULATING HORMONE LEVELS ON THE SECRETION OF THYROID HORMONES IN MAN
Authors: Carpi A. , Bianchi R. , Zucchelli G. C. , Del Corso L. , Levanti C. , Cocci F. , Giannessi D. , Mariani G.
Published: December 2008

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3, T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio betwen the serum levels of T3 and T4 (T3/T4), both within each patient group (P < 0.001) and among all patients (P < 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.
THE BEHAVIOUR OF THE THYROIDAL IODIDE TRAP AFTER SUBTOTAL THYROIDECTOMY FOR THYROTOXICOSIS AND ITS IMPLICATION FOR THE T3-SUPPRESSION TEST
Authors: Wilkin T. J. , Gunn A. , Isles T. E. , Crooks J. , Beck J. Swanson
Published: December 2008

It is important to distinguish between symptomatic response and immunological cure in thyrotoxicosis because it has been suggested that surgery, in addition to providing a rapid symptomatic response, may also cause the disappearance of thyroid-stimulating antibodies. The evidence, however, is based largely on suppression tests which we argue may not be valid in the post-operative period.

Seventy thyrotoxicosis patients were treated for 6 months with a standard course of carbimazole and T3, at the end of which each patient was classified as suppressor (S) or non-suppressor (NS) according to the fall in radioiodine uptake. Group I (18 patients) and group 11 (18 patients) were then randomly selected for immediate surgery while group III (34 patients) continued on antithyroid drugs. All groups were reviewed every two months from the 6th month for 12 months, during which time group I was drug-free and groups II and III received T3. Twenty-min iodide uptakes were performed in all patients at each visit to compare the serial changes in mean iodide trapping capacity between treatment groups. Despite 10-fold differences in TSH levels between groups I and II, and irrespective of suppressibility before surgery, the mean uptakes in both these groups remained basal (< 4 %) throughout the period of study, while the serial mean uptakes in group III S (no TSH, by implication no TSAB, but intact iodide trap) were consistently higher than those of group I NS (high TSH, by implication TSAB as well, but reduced iodide trap size).

The data points to an absence of dose-responsiveness between TSH and the surgical-remnant's iodide trap, implying that post-thyroidectomy suppression tests (at least during the first year) cannot measure changes in iodide trapping, and therefore do not measure the same phenomenon after subtotal thyroidectomy as they do before operation when the thyroid is intact. We therefore question the validity of comparing suppressibility before and after surgery and basing the frequency of surgical cure on the result.
EFFECT OF RAPID VARIATION OF RENAL FUNCTION ON PLASMA CALCITONIN AND PARATHYROID HORMONE IN MAN
Authors: Fuss M. , Bergans A. , Geurts J. , Brauman H. , Corvilain J.
Published: December 2008

Plasma levels of immunoreactive calcitonin (iCT) and parathyroid hormone (iPTH) have been measured sequentially in 6 patients following successful renal transplantation (RT) and in 3 patients during the recovery phase of acute renal failure (ARF). iCT and iPTH returned to normal values within a few days when glomerular filtration improved; both hormones rose in cases of acute graft rejection. Unlike iPTH iCT did not follow closely the variations of creatinine, iCT even rising before creatinine in one graft rejection. These observations could possibly be explained by a dissociation between the renal metabolism of iCT and the glomerular filtration.
THE ANDROGENS IN THE GUINEA-PIG FOETUS THROUGHOUT THE EMBRYONIC DEVELOPMENT
Authors: Rigaudière N.
Published: December 2008

Testosterone (T) and dihydrotestosterone (DHT) content and concentration were measured by radioimmunoassay in plasma, gonads, adrenals, and sexual ducts of 235 male and 214 female guinea-pig foetuses at various stages of gestation after gonadal and adrenal differentiation occurred.

In the male foetus, a sharp increase in the content and concentration of T and, to a lesser degree of DHT, is observed in the testis, the plasma and the ducts at the time of sexual differentiation between days 28 and 36. Thereafter androgen concentrations in these tissues decrease and rise again after day 52. In the female foetus, levels of T and DHT in the ovary are low throughout foetal life and do not account for the relatively high concentrations found in the plasma; in sexual ducts, T concentrations decrease at the time of differentiation. DHT levels are low at every stage. In both sexes, T and DHT are present in the adrenal. No sexual dimorphism is observed in the evolution of T and DHT adrenal content and concentration.