bluuebunny/crossref_metadata_2025 huggingface dataset:
BLOOD LIPIDS DURING TREATMENT OF HYPERTHYROIDISM
Authors: Jacobsen Bendt Brock
Published: December 2008

Thirty patients with newly diagnosed hyperthyroidism were examined with regard to a unified analysis of the relationship between the changes in lipid metabolism and the thyroid function. Before and after one week's treatment with thiamazol, determinations of the free fatty acids (FFA), glycerol, cholesterol, phospholipid, triglyceride and paper lipoprotein electrophoresis were made on venous blood, together with determinations of PBI, T4, T3 test and basal metabolic rate (BMR).

The FFA and glycerol concentrations were increased, but not correlated in the untreated patients. During treatment the lipolysis decreased in step with the fall in thyroid function and BMR. The concentrations of cholesterol, phospholipid and triglyceride were well correlated in the untreated patients. During the treatment the serum cholesterol rose significantly, while the rise in phospholipid and triglyceride was less pronounced. The changes were related with the changes in the T3 test. The rise occurred more frequently in patients with goitre. The lipid changes could not be demonstrated by the technique of lipoprotein electrophoresis used. Thus FFA, glycerol and to a lesser extent cholesterol in the blood are sensitive indicators of the antithyroid treatment.
STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY (SEIP-BERARDINELLI SYNDROME)
Authors: Oseid Svein
Published: December 2008

Six cases of congenital generalized lipodystrophy have been studied at different ages from infancy to adolescence with regard to glucose tolerance, insulin secretion, and insulin sensitivity. During the first few years of life there is normal glucose tolerance. The fasting immuno-reactive insulin (IRI) levels are either slightly elevated or normal. The IRI response to glucose is exaggerated and prolonged, at least from the third year of life. Some degree of insulin resistance is already present in infancy.

From the age of 8–10 years glucose tolerance decreases rapidly. The fasting IRI levels are usually grossly elevated, while fasting plasma glucose levels are only moderately elevated or normal. The IRI responses to oral and iv administered glucose, and to tolbutamide are exaggerated; the insulinogenic indices are high. Cortisone primed glucose tolerance tests become abnormal. Insulin resistance is marked, and increases with age.

After cessation of growth at approximately 12 years of age, frank diabetes with fasting hyperglycaemia and diabetic glucose tolerance curves developed in the one patient followed beyond this age. Her fasting IRI was increased, but there was a poor IRI response to glucose stimulation, suggesting a partial exhaustion of the β-cells. Her initial IRI response to tolbutamide was still good, but not as brisk as in the younger patients. This type of diabetes is quite different from the juvenile form, and also from the diabetes of older age. It may be causally related to the lack of an adequate adipose organ necessary for the disposal of excesses of glucose, or possibly related to another anti-insulin mechanism.
ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN
Authors: Widström A. , Cerasi E.
Published: December 2008

The plasma insulin response to intravenously administered tolbutamide was measured in healthy subjects under experimentally induced variations in the blood glucose concentration. Decreasing blood glucose concentration down to 51 and 25% of the basal level by the iv administration of 0.05 and 0.10 IU of insulin/kg body weight, respectively, resulted in significant inhibition of the insulin response to tolbutamide. The degree of inhibition was correlated to the extent of the hypoglycaemia. This inhibition seems to be only partially mediated by catecholamines, since blocking the α-adrenergic receptors with phentolamine could not restore the action of tolbutamide. Furthermore, whereas the prevention of the hypoglycaemia that normally follows tolbutamide administration resulted in an enhancement of the insulin response to the drug, phentolamine had no such effect. These results indicate that the decrease in blood glucose concentration as such, rather than activation of the adrenergic mechanisms, is responsible for the inhibition of tolbutamide-induced insulin release. Hence, the blood glucose level at the time of tolbutamide administration seems to determine the insulin response to the drug.

The administration of the β-adrenergic blocking agent propranolol, in doses known to suppress glucose-induced insulin release in man, had no effect on the insulin response to tolbutamide. Our studies thus do not confirm the reports of other investigators that sulphonylureas may act on the islet cell as β-adrenergic agonists.
THE EFFECTS OF OVARIAN STEROIDS ON FOOD AND WATER INTAKE AND BODY WEIGHT IN THE FEMALE RAT
Authors: Tarttelin M. F. , Gorski R. A.
Published: December 2008

The influence of ovarian steroids on food intake (FI), water intake (WI) and body weight (BWt) was measured under various conditions. Ovariectomy results in an increase in FI and BWt, which plateaued around one month after surgery. Daily injection of 1.5 μg oestradiol benzoate (OB) initiated at this time significantly reduced both FI and BWt. This effect of daily OB treatment on FI is only transitory since the FI returns to normal during OB treatment although the effect on BWt is maintained throughout and beyond OB treatment. Following ovariectomy, WI gradually falls, but is returned to normal by daily OB treatment. When oestrogen treatment is initiated at the time of ovariectomy, the increase in FI and BWt is prevented. In additional ovariectomized rats, 3 μg OB was injected every fifth day with either progesterone or oil administered on the intervening days. Although no influence of progesterone injection (either with OB or alone) was detected, the intermittent injection of OB induced cyclic suppression of FI, and the pattern of FI approached that of the intact cycling female. Adaptation to the intermittent injection of OB was not observed. Finally, OB treatment was found to decrease the increased FI seen during pseudopregnancy by a proportion similar to the effect of oestrogen in the long-term ovariectomized animal. These results suggest that oestrogen, but not progesterone, is the ovarian hormone active in the regulation of intake parameters and body weight in the female rat.
THE EFFECT OF AN OESTROGENIC STEROID ON THE SECONDARY IMMUNE RESPONSE UNDER DIFFERENT HORMONAL ENVIRONMENTS
Authors: Thanavala Yasmin M. , Rao Shanta S. , Thakur A. N.
Published: December 2008

The effect of mestranol was studied on the secondary antibody response in mice under different hormonal environments. The results revealed that in the intact and ovariectomized animals treated with the oestrogen, the antibody response was of the parabolic type. In adrenalectomized mice, the administration of the steroid resulted in appreciably elevated levels of anti-tetanus antibodies. The response obtained was similar in animals receiving both the low and high doses of the oestrogen. Removal of both the ovaries and the adrenals resulted in marked increases in the antibody levels.

Thus mestranol exerts an enhancing effect on the secondary antibody response in mice. This enhancement is, however, modified and regulated by the endogenous ovarian and adrenal hormones.
CLINICAL EXPERIENCE WITH THE THYROTROPHIN RELEASING HORMONE (TRH) STIMULATION TEST IN PATIENTS WITH THYROID, PITUITARY AND HYPOTHALAMIC DISORDERS
Authors: Karlberg Bengt E. , Almqvist Sven
Published: December 2008

The clinical value of a standardized iv TRH-stimulation test was studied in 96 patients with thyroid, pituitary and hypothalamic disorders.

A lack of TSH-response to TRH, 50–200 μg iv was observed in 38 patients with overt hyperthyroidism. Nor was there any response in three clinically euthyroid patients with suspected hyperthyroidism, normal routine thyroid tests and failing suppressibility after the administration of T3 or T4.

Twenty-one patients with primary hypothyroidism had high basal TSH-levels (mean ± sem = 85.6 ±12 μU/ml).

Furthermore, a prolonged TSH-response was characteristic of this group. No correlation was found between the degrees of clinical hypofunction and basal TSH or TSH-responses.

Nine patients with hypothyroidism secondary to pituitary lesions did not respond to TRH-stimulation.

In clinically euthyroid patients with pituitary chromophobe adenomas, two exhibited normal and five impaired TSH-responses.

Nine out of 12 patients with active acromegaly showed no or impaired TSH-response, and, on an average, there was a slight increase in the serum TSH at 20 minutes in response to TRH. A several-fold increase in serum STH occurred after TRH in five acromegalic patients.

A normal TSH-response was obtained in four of six patients with hypothalamic lesions.

In conclusion, the TRH-stimulation test is of special clinical value in patients with hyperthyroidism (no response), in discriminating between primary and secondary hypothyroidism and in assessing the functional pituitary TSH-reserve in pituitary and hypothalamic lesions.
EFFECTS OF GONADOTROPHINS AND CYCLIC 3′,5′-AMP ON IN VITRO INCORPORATION OF [3H]URIDINE INTO RNA OF THE PREPUBERTAL RAT OVARY
Authors: Jarlstedt Jan , Nilsson Lars , Hamberger Lars , Ahrén Kurt
Published: December 2008

In vivo and in vitro effects of FSH and LH on in vitro incorporation of [3H]uridine into RNA of the prepubertal rat ovary have been studied. RNA was fractionated with composite agarose-polyacrylamide gel electrophoresis. When FSH was injected into the prepubertal rats 4 h before incubation of the ovaries, the incorporation of labelled uridine into total RNA was decreased showing relatively more radioactivity concentrated to the RNA fractions lighter than 28S as compared to the controls. These effects were not seen when FSH was added to the incubation medium in vitro. When LH was added in vitro to the isolated ovaries a higher percentage of incorporated radioactivity was concentrated in the RNA fractions heavier than 28S without any change in the incorporation of [3H]uridine into total RNA. LH administered in vivo 30 min before incubation of the ovaries gave the same change in the labelling pattern between the RNA fractions as LH in vitro but in addition showed a decreased incorporation of radioactivity into total RNA.

The in vitro effects of cyclic 3′,5′-AMP were also studied. When prepubertal rat ovaries were incubated in 10 mmol/l of this cyclic nucleotide, the incorporation of [3H] uridine into total RNA was decreased without any change in the labelling pattern.
TESTOSTERONE AND OESTRADIOL SUPPRESSION OF LH AND FSH IN ADULT MALE RATS: DURATION OF CASTRATION, DURATION OF TREATMENT AND COMBINED TREATMENT
Authors: Swerdloff R. S. , Walsh P. C.
Published: December 2008

The effects of androgens and oestrogens on serum LH and FSH in castrated rats were evaluated with regard to the modifying influences of duration of castration, duration of treatment and combined oestrogen-androgen effect. Serum LH was not greatly influenced by these variables. In contrast, serum FSH was shown to be more resistant to suppression by both steroids after at least five days of castration, requiring a longer duration of treatment to be suppressed to intact levels. Combined treatment of submaximally suppressive doses of testosterone propionate and oestradiol benzoate resulted in no additive effect on lowering serum FSH. Low doses of both androgens and oestrogens resulted in elevated levels of serum LH and FSH, suggesting that the adult male hypothalamic-pituitary axis may be responsive to positive feedback. In all studies, testosterone preferentially suppressed serum LH as compared to serum FSH. In contrast, oestradiol administration produced parallel inhibition of both LH and FSH. It is emphasized that neither oestrogen nor androgen alone, nor in combination, resulted in preferential inhibition of serum FSH over LH.
URINARY METABOLITES OF DL-NORGESTREL IN WOMEN
Authors: Sisenwine Samuel F. , Kimmel Hazel B. , Liu Ann L. , Ruelius Hans W.
Published: December 2008

Urines obtained from women administered the totally synthetic progestational steroid, 14C-dl-norgestrel, were fractionated on DEAE-Sephadex A-25. This anion exchanger separated unchanged norgestrel and ether extractable metabolites (6.5–10.2 % of the urinary radioactivity) as well as neutral, non-extractable metabolites (4.0–12.3 % of the urinary radioactivity) from anionic conjugates of norgestrel and its metabolites (75.8–88.8 % of the urinary radioactivity). The latter, in turn, were separated into seven fractions. One fraction, after solvolysis, was found to contain only the major metabolite, 16β-hydroxynorgestrel as sulphate(s) (approximately 30 % of the urinary activity). The remaining conjugated fractions as well as the free fraction were analyzed, and at least 23 metabolites were detected. Among them were biotransformation products resulting from hydroxylation at the 16α, 16β, 1β, 2α and 6ε position, D-homoannulation and ring-A reduction (3α,5β-tetrahydronorgestrel and its 3β, 5β and 3α, 5α isomers and a 16-hydroxylated tetrahydronorgestrel). Structures of the major metabolites were confirmed by mass spectrometry.
NEW SYNTHETIC STEROIDS WHICH INHIBIT RAT GONADAL STEROIDOGENIC ENZYMES BOTH IN VITRO AND IN VIVO
Authors: Goldman Allen S. , Gustafsson Jan-Åke , Gustafsson Sven A.
Published: December 2008

Six different steroidal analogues with previously suggested effects on gonadal Δ5,3β-hydroxysteroid oxidoreductase, 17α-hydroxylase and C17-20 lyase were investigated in vitro and in vivo. Testicular microsomal conversion of dehydroepiandrosterone to androstenedione and testosterone and of pregnenolone to progesterone and 5α-pregnane-3,20-dione was used as an index of Δ5,3β-hydroxysteroid oxidoreductase activity. 17α-hydroxylase activity was estimated from testicular microsomal formation of 17α-hydroxyprogesterone, androstenedione and testosterone from progesterone and the activity of C17-20 lyase was determined from the conversion of 17α-hydroxyprogesterone into androstenedione and testosterone.

Analysis by gas-liquid chromatography – mass spectrometry of the steroidal excretion patterns in urine and faeces from female rats treated with two inhibitors of 17α-hydroxylase and C17-20 lyase in vivo, (I) 16β-bromo-3β,17α-dihydroxy-5α-pregnane-11,20-dione and (II) 17β-ureido-1,4-androstadien-3-one, and a third inhibitor (VI) 17α-cyano-5-androstene-3β,17β-diol, which also inhibits Δ5,3β-hydroxysteroid oxidoreductase in vitro, demonstrates the absence of C19 steroids of ovarian origin. C19 steroids are not excreted by rats treated with I and II up to 7 days after the last dose suggesting that the effects of these inhibitors are persistent. Two other steroids (III) 17-cyano-5,16-androstadien-3β-ol 3-acetate and (V) 17-cyano-5,16-androstadien-3β-ol, inhibit Δ5,3β-hydroxysteroid oxidoreductase in vitro in addition to 17α-hydroxylase and C17-20 lyase and cause the abnormal appearance of Δ5,3β-hydroxy-C19 steroids in the urines of normal and adrenalectomized females but not in those of ovariectomized or in ovariectomized and adrenalectomized rats. Each of these inhibitors also eliminates urinary 3α,17α-dihydroxy-5α-pregnan-20-one of ovarian origin.

The pattern of C21O4 and C21O5 steroids of adrenal origin was only slightly affected or not affected at all by I–III and V and VI. The steroidal excretion patterns obtained in treated animals indicate a predominantly ovarian site of action of these inhibitors in vivo. Thus, the present results indicate three agents which block sex hormone production in the rat and two which inhibit gonadal Δ5,3β-hydroxysteroid oxidoreductase with moderate or no inhibition of the adrenal excretion.
THE TESTIS IN PATIENTS WITH ABNORMALITIES OF SEX DIFFERENTIATION. HISTOLOGY AND ENDOCRINE FUNCTION
Authors: Neto R. Sandrini , Rivarola M. A. , Coco R. , Bergadá C.
Published: December 2008

Testicular function was studied in 18 patients with abnormalities of sexual differentiation. Fourteen patients were prepubertal and four postpubertal. Plasma testosterone was determined before and after 5000 IU HCG administered daily during 5' days. Of the fourteen prepubertal patients, the two true hermaphrodites and the patient with asymmetrical gonadal differentiation showed a poor response to gonadotrophin stimulation. This could be explained by the small amount of active testicular tissue or its coexistence with ovarian and rudimentary gonadal tissue which might exert some influence on the endocrine function of the testis. In the group of eight patients with male pseudo-hermaphroditism and ambiguous external genitalia, the response to HCG showed a large variation. The three patients with small testes had lowest values i. e. 210, 198 and 192 ng/100 ml. The remaining five patients showed normal values ranging between 360 and 720 ng/100 ml. The ambiguous external genitalia of these patients could be explained as being due to a diminished androgen target organ sensitivity limited to the external genitalia. The three prepubertal patients with male pseudo-hermaphroditism and female external genitalia showed a marked increase in plasma testosterone with HCG ranging between 598 and 1100 ng/100 ml. The four pubertal cases also had high values in basal conditions, between 920 and 1870, which increased even more after gonadotrophin stimulation, in one case from 1382 to 2264 ng/100 ml. This hypersensitivity to exogenous HCG, even in infancy, correlates with the elevated basal values observed in adult patients with otherwise female external genitalia and androgen insensitivity. Finally, the HCG stimulation test could be useful for the demonstration of testicular tissue in prepubertal patient with abnormalities of sexual differentiation, although it cannot be used as a prognosis of masculinization or feminization at puberty.
PITUITARY AND GONADAL FUNCTION IN HYPOGONADOTROPHIC HYPOGONADISM
Authors: Espiner E. A. , Donald R. A.
Published: December 2008

Hypothalamic-pituitary function and gonadal histology and responsiveness have been assessed in three patients with isolated deficiency of gonadotrophin secretion. Gonadotrophin secretion was uniformly reduced and sex steroid excretion markedly impaired in all three cases. Biopsy of the gonad showed immature glands and no increment in steroid excretion resulted from stimulation using human chorionic gonadotrophin. No response in gonadotrophins to clomiphene occurred in 2 of the 3 patients tested. Whereas normal ACTH and adrenal response to hypoglycaemic stress and metopirone was shown in 2 of the 3 cases, the increment in growth hormone secretion was reduced. Following sex steroid therapy, the growth hormone response was improved and increased ACTH release during hypoglycaemia was observed in one patient. No change in gonadotrophin secretion occurred during longterm sex steroid therapy.
THE EFFECT OF DIHYDROERGOTAMINE ON ACTH-STIMULATED LIPOLYSIS IN RAT ADIPOCYTES
Authors: Kowadlo-Silbergeld Avivah , Klipper Yaffa , Laron Zvi
Published: December 2008

Isolated fat cells prepared from epididymal adipose tissue of fasted rats were incubated in Krebs Henseleit bicarbonate buffer containing 3 % albumin and 0.5 mg/ml glucose. The effect of dihydroergotamine (DHE), 8 μg/ml, on the lipolysis stimulated by synthetic β1-24 ACTH was assessed by the glycerol or free fatty acid (FFA) release into the medium.

DHE potentiated ACTH-stimulated lipolysis over a dose range of 10−10 to 10−3 U/ml. The maximal degree of potentiation was observed between 15 and 30 min incubation time. The critical period during which the addition of DHE to cells incubated with ACTH still produced the optimal effect was 4 to 7.5 min. However, when ACTH was added to cells incubated for up to 2 h with DHE, lipolysis was still significantly enhanced. Preincubation of cells in DHE followed by resuspension in fresh medium not containing DHE produced response to ACTH which far exceeded that obtained by any other incubation procedure with the alkaloid used in the same experiment. DHE may have multiple effects on the fat cell of the rat, at low doses (10−7 m to 10−5 m by acting as an inhibitor of phosphodiesterase or as a potentiator of cyclic AMP, or at higher doses, as a non-specific inhibitor of hormone induced lipolysis.
THE ROLE OF A FEEDBACK MECHANISM IN THE REGULATION OF ALDOSTERONE SECRETION IN THE RAT
Authors: Debreceni L. , Csete B.
Published: December 2008

The effect of prolonged aldosterone and DOC treatment in the in vitro aldosterone production was studied in the rat. When the animals were supplied with food containing 16.5 mEq./100 g of sodium, both aldosterone and DOC treatment led to a marked decrease in aldosterone production. On the other hand, under dietary sodium restriction both aldosterone and DOC treatment failed to induce a suppression of the elevated aldosterone production. On the basis of these findings, it seems that a sufficient sodium supply of the organism is necessary for the control of aldosterone secretion either by an increase of aldosterone production or DOC treatment if any feedback regulation is involved in the mechanism controlling aldosterone secretion.
ANTIBODIES TO PROINSULIN IN DIABETIC PATIENTS TREATED WITH PORCINE INSULIN PREPARATIONS
Authors: Andersen O. Ortved
Published: December 2008

In most diabetic patients treatment with commercial insulin preparations containing 1 to 2 per cent proinsulin, results primarily in the formation of antibodies reacting with both insulin and proinsulin. Later on the formation of antibodies reacting specifically with proinsulin also seems to occur. In some plasma samples from patients treated with porcine insulin it has been possible to demonstrate the formation of antibodies reacting with proinsulin and intermediate forms, but not with monocomponent insulin, dimer forms or C-peptide from porcine insulin. No reaction of bovine proinsulin with antibodies to porcine proinsulin could be demonstrated.

The observations indicate that proinsulin has considerable significance for antibody formation in diabetic patients treated with the commonly available insulin preparations.
STUDIES ON SUSTAINED CONTRACEPTIVE EFFECTS WITH SUBCUTANEOUS POLYDIMETHYLSILOXANE IMPLANTS
Authors: Benagiano G. , Ermini M. , Carenza L. , Donini P.
Published: December 2008

Ovarian function was assessed in 10 healthy young women, before and after the insertion of 3 or 4 polydimethylsiloxane capsules filled with 20 mg of megestrol acetate. Each capsule released in vitro, approximately 20 μg/24 h of the hormone.

Daily determination of the urinary excretion of FSH, LH, fractionated oestrogens and pregnanediol were performed in all subjects during one control cycle, the first and the third cycle after the insertion of the capsules. Out of 10, 8 control cycles were ovulatory according to all the parameters investigated. This compares with 15 ovulatory cycles out of a total of 20, examined after the insertion of the capsules.

During treatment no changes were observed in the FSH excretion pattern; the mid-cycle LH peak was present in all ovulatory cycles, although it was usually much less evident under the action of megestrol acetate. The excretion of oestradiol was significantly increased in all subjects (P < 0.05) during the first cycle following implantation. Oestrone and oestriol excretion was also generally higher in patients bearing PDS capsules; however, this difference was not statistically significant. Pregnanediol levels were not affected by the treatment in all cycles considered to be ovulatory on the basis of all the parameters.

The menstrual bleeding pattern did not change in the majority of cases. One patient had, during treatment with 3 capsules, two profuse break-through bleedings whereas another one became amenorrhoic two months after the insertion of 4 implants.

It is concluded that megestrol acetate sustained release preparations do not inhibit ovulation under the experimental conditions used.
HETEROGENEITY OF LONG ACTING THYROID STIMULATING (LATS) – ACTIVITY, THYROGLOBULIN ANTIBODIES AND THYROID MICROSOMAL ANTIBODIES
Authors: Adlkofer F. , Schleusener H. , Uher L. , Ananos A. , Brammeier C.
Published: December 2008

Crude IgG of sera from 3 patients with Graves' disease, which contained LATS-activity and/or thyroid antibodies, was fractionated by isoelectric focusing in a pH-range between 6.0 to 10.0. LATS-activity was found in IgG-subfractions from pH 7.5 to 9.5, thyroglobulin antibodies and thyroid microsomal antibodies from pH 6.0 to 10.0. It was not possible to separate LATS-activity from the thyroid antibodies by this technique. The results indicate that LATS and the thyroid antibodies are heterogeneous and of polyclonal origin.
DIFFERENTIAL ACTION OF PARATHYROID AND THYROID HORMONES ON EFFECTIVE INTESTINAL ABSORPTION OF CALCIUM
Authors: Hehrmann R. , Hagemann J. , Montz R. , Jentsch E.
Published: December 2008

The effects of parathyroidectomy (PTX) and radio-thyroidectomy (131I-TX) as well as the actions of parathyroid extract (PTE), dibutyryl cyclic adenosine monophosphate (DBcAMP), calcitonin (CT) and thyroid extract (thyreoidea sicca) on effective intestinal calcium absorption in intact, PTX and 131I-TX rats were evaluated by a new, physiological in vivo method. Ten hours after the administration of 47calcium labelled food the animals were killed and the entire intestine was removed. Whole body retention of 47calcium was measured allowing the calculation of the effective intestinal absorption of calcium (true absorption minus excretion within ten hours).

The known actions of PTE and DBcAMP were confirmed by this method. CT did not exert a direct effect in any of the experimental groups.

The absence of thyroid hormones (TX rats) remarkably reduced effective calcium absorption. In the presence of endogenous parathyroid hormone (PTH) (TX rats) the administration of minimal amounts of thyroid hormones was sufficient to increase effective calcium absorption, whereas PTE and DBcAMP did not have any effect. In the absence of PTH (TX-PTX rats) thyroid hormones did not enhance effective absorption, indicating, that thyroid hormones alone do not stimulate the effective absorption of calcium.

It is concluded, that the thyroid hormones act indirectly, as a permissive agent, enabling PTH to exert its active stimulating effect on the effective intestinal absorption of calcium.
VARIATIONS IN PLASMA ALDOSTERONE AND PLASMA RENIN ACTIVITY THROUGHOUT THE MENSTRUAL CYCLE, WITH SPECIAL REFERENCE TO THE PRE-OVULATORY PERIOD
Authors: Sundsfjord Johan A. , Aakvaag A.
Published: December 2008

The day to day variations in plasma aldosterone and plasma renin activity throughout the menstrual cycle have been investigated in healthy young women. A sensitive and specific radioimmunoassay for the measurement of plasma aldosterone is described. The actual hormone parameters have been correlated with fluctuations in plasma oestradiol and progesterone, and LH has been measured for the determination of time of ovulation.

Plasma renin activity and plasma aldosterone gradually increased two to four times from the early follicular to the mid-luteal phase, in accordance with earlier observations.

In one woman using a beta adrenergic blocking agent plasma renin activity rose only slightly, whereas a normal rise in plasma aldosterone was noted.

Another woman became pregnant during the cycle investigated. In this subject neither plasma renin activity nor plasma aldosterone decreased at the end of the cycle.

Plasma aldosterone was almost doubled on the pre-ovulatory day, as compared with the early follicular phase, whereas no significant change in plasma renin activity or plasma renin substrate was found. The cause of this pre-ovulatory increase in plasma aldosterone is not known.
GAS CHROMATOGRAPHIC AND MASS SPECTROMETRIC STUDIES ON OESTROGENS IN BILE: PART I. PREGNANT WOMEN
Authors: Adlercreutz H. , Ervast H.-S. , Tenhunen A. , Tikkanen M. J.
Published: December 2008

Qualitative and quantitative studies on oestrogens by gas chromatography and mass spectrometry were carried out on samples of pregnancy bile obtained in the 10th to the 33rd week of gestation by duodenal intubation, puncture of the gall-bladder during operation, or by T-tube drainage of the main bile duct. After hydrolysis of the conjugates the identity of the following oestrogens was established: Oestriol, oestrone, 2-methoxy-oestrone, oestradiol-17β, 11-dehydro-oestradiol-17α, 16-epioestriol, 17-epioestriol, 16α-hydroxyoestrone, 16β-hydroxyoestrone, 16-oxo-oestradiol17β, 15α-hydroxyoestrone and 15α-hydroxyoestriol. In addition oestradiol-17α was detected. The quantitative analyses revealed that all oestrogens seem to occur in higher concentrations in the bile than in plasma. Very high levels of 16α-hydroxyoestrone were found and in one bile sample the value exceeded that of oestriol. The concentration of 16β-hydroxyoestrone was about 100 times greater than that found in maternal plasma and 15α-hydroxyoestrone also occurred in much greater amounts in the bile than in plasma. The composition of oestriol conjugates was determined in two bile samples. Oestriol-3-sulphate,16-glucosiduronate comprised the largest fraction (77 and 62 %), followed by oestriol-16-glucosiduronate (21 and 36%) and minute amounts of oestriol-3-sulphate (1.7 and 2.5%). Generally, the pattern of oestrogens in bile during pregnancy differs very much from that seen in other biological fluids and seems to reflect the metabolic activities of the liver cells.
TESTOSTERONE METABOLISM IN SUBCELLULAR FRACTIONS OF RAT PROSTATE
Authors: Nozu Kaoru , Tamaoki Bun-ichi
Published: December 2008

Homogenates of rat ventral prostates were fractionated into the nuclear (purified from the precipitate at 800× g), mitochondrial (precipitate at 1000–6000 ×g), microsomal (precipitate at 10 000–105 000× g) and cytosol (supernatant fluid at 105 000 × g) fractions, which were morphologically identified under an electron-microscope. Among the subcellular fractions, the highest specific activity of Δ4-5α-hydrogenase was localized in the nuclear and microsomal fractions, while 3α-hydroxysteroid dehydrogenase (E. C. 1. 1. 1.50) activity was concentrated exclusively in the cytosol fraction. By addition of the cytosol fraction, the Δ4-5α-hydrogenase activity in the microsomal fraction was markedly reduced, whereas the activity in the nuclear fraction was scarcely inhibited. By heating the cytosol fraction at 100°C for 20 min, its inhibitory effect was significantly diminished. The inhibitory principle in the cytosol fraction against the Δ4-5α-hydrogenase was mostly concentrated in the precipitate at 0–60% saturation of ammonium sulphate, while the major activity of the 3α-hydroxysteroid dehydrogenase was localized in the precipitate at 40–100% saturation of the salt. According to the enzyme kinetics, the cytosol 0–40 % fraction showed the competitive type of inhibition with the Δ4-5α-hydrogenase activity in the microsomal fraction for testosterone.
CHANGES IN PLASMA LEVELS OF PROLACTIN AND LH INDUCED BY LUTEOLYTIC OR LUTEOTROPHIC TREATMENT IN INTACT CYCLING SHEEP AFTER SECTION OF THE PITUITARY STALK
Authors: Kann G. , Denamur R.
Published: December 2008

Oestradiol has been shown to cause either premature luteal regression or prolonged luteal maintenance depending on whether it is administered early or late in the oestrous cycle. Although these effects are not observable in the absence of the uterus, it was considered desirable to examine the possibility that the pituitary gland as well as the uterus may be involved in this phenomenon. Accordingly, plasma LH and prolactin concentrations were studied in sheep treated with oestradiol from day 3 (luteotrophic action) or day 11 (luteolytic action) with and without pituitary stalk section. Plasma LH fell below the limit of detection (0.3 ng/ml) in the plasma of sheep after pituitary stalk section, whether or not oestradiol had been administered. In the intact ewe, oestradiol given from day 3 resulted in luteal maintenance associated with a significant increase in the secretion of plasma LH and prolactin. However, similar treatment in the stalk sectioned ewe also resulted in luteal maintenance without any major increase in gonadotrophin secretion. On the other hand, when oestradiol was given from day 11, there was no evidence either from the intact or the stalk sectioned sheep that the pituitary contributed to the luteolytic action of oestradiol may possibly have a pituitary component, the luteolytic action is probably mediated solely by the oestrogenic action on the uterus.
COMPARATIVE EXPERIMENTS ON THE URINARY EXCRETION OF EXOGENOUS OXYTOCIN AND VASOPRESSIN
Authors: Jensen Svend Erik , Frandsen Per , Nielsen Aage Theil
Published: December 2008

The urinary excretion of oxytocin (milk-ejecting activity) and arginine vasopressin (antidiuretic activity) in water-loaded rabbits was measured following simultaneous intravenous injection of 1–9 IU of oxytocin and 0.1–0.3 IU of vasopressin per animal. The percentage excretion of vasopressin was 2–10 times that of oxytocin.

Experiments with a steady state blood level of vasopressin and oxytocin maintained by continuous infusion showed, that the vasopressin/oxytocin ratio increased 2–6 times, when the hormones passed from the blood into the urine. This indicates a difference in the renal handling of the hormones with regard to the mechanism of the urinary excretion.

The urinary clearance of vasopressin was about the same as that of inulin, consistent with the hypothesis, that vasopressin is excreted mainly by glomerular filtration. The clearance of oxytocin was lower than that of vasopressin and inulin, indicating that oxytocin is filtered at a lower rate (binding to plasma proteins) or partly re-absorbed or inactivated in the tubules and/or collecting ducts.
EFFECT OF DEXAMETHASONE ON ADRENOCORTICAL RESPONSES IN INTACT AND HYPOTHALAMIC DEAFFERENTED RATS
Authors: Feldman S. , Conforti N. , Chowers I.
Published: December 2008

The effects of systemically administered dexamethasone on adrenocortical responses to ether stress were studied in intact and in hypothalamic deafferented rats, in which a hypothalamic island was produced. The inhibitory effect of dexamethasone was twice as marked in the intact animals than in the rats with hypothalamic islands. However, direct implantation of dexamethasone into the mediobasal hypothalamus depressed the adrenocortical responses to the same extent in the intact and the deafferented rats. These results would indicate that the negative feedback of dexamethasone in the regulation of ACTH secretion is exerted at hypothalamic levels and that other extra-hypothalamic structures also participate in this mechanism.
IN VITRO CONVERSION OF [4-14C] DEHYDROEPIANDROSTERONE AND ANDROSTENEDIONE TO OESTROGENS BY THE MICROSOMES OF PLACENTAS FROM NORMAL, TOXAEMIC, DIABETIC AND POSTMATURE PREGNANCIES
Authors: Lehmann W. D. , Lauritzen Ch. , Schumann R.
Published: December 2008

The placental oestrogen precursors [4-14C]dehydroepiandrosterone (DHA) and [4-14C]androstenedione (AD) were incubated with microsomal fractions of human placentas from normal and pathological pregnancies at different stages of gestation, in order to evaluate the rate of conversion of the substrates to oestrogens. In placentas from normal pregnancies the capability to convert C19-steroids (DHA and AD) to C18-steroids (oestrone and oestradiol017β) increased with the age of gestation. The placenta at term metabolizes [4-14C]DHA and [4-14C]AD into oestrogens (oestrone and oestradiol-17β) with a four times greater aromatisation rate than the placenta at midpregnancy. The concentration of protein in the placental microsomal fraction also increased with the age of gestation. In our aromatisation studies it was found that the conversion rate of DHA and AD to oestrogens (oestrone and oestradiol-17β) by placental microsomes was significantly lowered in toxaemic and diabetic placentas and in placentas of postmaturity cases as compared to normal placentas at term. The relationship between placental insufficiency and a lowered capacity of Δ5-Δ4-isomerase, 3β-hydroxysteriod-dehydrogenase and the aromatizing enzyme systems is discussed with regard to the main causes of a low oestriol excretion and a low aromatisation rate of injected DHA-S in pathological pregnancies. Finally it is shown, that the parameters of the hormonal investigations correlate with the degree of pathological microscopic alterations of the placentas.
URINARY EXCRETION OF FREE CORTISOL IN HYPERCALCAEMIA
Authors: Jorgensen F. Schønau , Kehlet H.
Published: December 2008

Human and animal studies have uniformly demonstrated increased hypothalamic-pituitary-adrenocortical (HPA) activity during acute hypercalcaemia. The HPA-activity during chronic hypercalcaemia was investigated by means of free urinary cortisol excretion. No difference in HPA activity could be demonstrated between a hyperparathyroid hypercalcaemic and a normocalcaemic group of patients. Based on these results it is suggested that during chronic hypercalcaemia, the HPA feed back mechanism overcomes the influence of hypercalcaemia on the HPA-axis.
FEMALE ENDOCRINE CONTROL MECHANISMS DURING THE NEONATAL PERIOD
Authors: Schulz K.-D. , August S.
Published: December 2008

The purpose of this paper is to report on the in vivo effect of different doses of cis- and trans-clomiphene on the RNA and protein synthesis in the ovary, liver, adrenal gland and uterus of newborn guinea pigs. After the sc injection of either isomer the biochemical parameters were determined at different time intervals. Both isomers induced an increase of the RNA- and protein-synthesizing activity in the uterus, but failed to do so in the ovary, liver and adrenal gland. According to data reported here and also by other investigators it may be assumed that the lack of ovarian response to the treatment with cis- or trans-clomiphene is primarily due to the functional immaturity of the female hypothalamus and/or pituitary during the neonatal period. Both isomers failed to modify the pattern of gonadotrophin release, as shown by the constancy of the ovarian RNA and protein synthesis after the administration of either of the isomers.

In the uterus, both cis- and trans-clomiphene strikingly imitated the biochemical stimulation produced by natural oestrogens. In contrast to oestradiol-17β, both clomiphene isomers showed a later onset and longer duration of the oestrogenic activity. The first increase of the amino acid incorporation into uterine proteins was noted after 5 hours in the cis-clomiphene treated group and after 8 hours in the trans-clomiphene treated animals as compared to 1 hour when oestradiol-17β was used. This difference seems to be due to a delayed transfer of the cytoplasmic oestradiol receptor to the nucleus after the injection of cis- or trans-clomiphene. As compared to oestradiol-treated animals, the clomiphene injection provoked a prolonged elevation of the uterine protein-synthesizing activity, most likely reflecting an effect of the enterohepatic recirculation of both isomers.
DETECTION OF [3H]5α-ANDROSTANE-3α,17β-DIOL AND [3H]17β-HYDROXY-5α-ANDROSTAN-3-ONE IN MOUSE TESTES FOLLOWING ADMINISTRATION OF [3H]TESTOSTERONE
Authors: Kasai Hisanori , Mizutani Shutaro , Matsumoto Keishi
Published: December 2008

[3H]Testosterone (2.0 μg/300 μCi or 3.3 μg/500 μCi) was injected into each of 23 mice, aged 45 days and the distribution of tritium among certain unconjugated steroids in the whole tissue, nuclear, mitochondrial + microsomal and cytosol fractions from the testes, liver, muscle, blood and prostate + seminal vesicle was determined 1 h after the injection.

[3H] 17β-Hydroxy-5α-androstan-3-one could be clearly shown in the whole tissue and the three fractions from the testes and prostate-seminal vesicle, but none was identified in any of the fractions from androgen-unresponsive tissues such as the liver, muscle and blood. However, the levels of [3H] 17β-hydroxy-5α-androstan-3-one were much higher in the prostate-seminal vesicle than in the testes. The levels of [3H]5α-androstane-3α,17β-diol in all the fractions from the testes as well as those from the prostate-seminal vesicle were in the order of ten times the levels in the corresponding fractions from the liver and muscle. Identification of [3H] steroids was accomplished by reverse isotope dilution and re-crystallization to constant specific activity. It would appear that the mouse testes belong to androgen-responsive tissues and that 5α-androstane-3α,17β-diol and 17β-hydroxy-5α-androstan-3-one may play a role in the testes.
THE HORMONAL CONTROL OF RIBONUCLEASE ACTIVITY IN THE LYMPHATIC TISSUE OF MICE
Authors: Maor D. , Eylan E. , Alexander P.
Published: December 2008

Ribonuclease activity in thymus and lymph nodes is stimulated by cortisone; insulin increases ribonuclease activity only in the thymus. Growth hormone and theophylline do not cause changes in thymus and lymph nodes ribonuclease levels. Injections of cortisone combined with growth hormone or with theophylline increase the activity more than cortisone alone. Insulin does not enhance the action of cortisone on ribonuclease activity. A synergistic loss in weight of thymus and spleen was found after administration of cortisone in combination with either growth hormone or with theophylline.
LOCALIZATION AND CONTENT OF THYROTROPHIN RELEASING FACTOR (TRF) IN MEDIAN EMINENCE OF THE HYPOTHALAMUS
Authors: Joseph Shirley Anne , Scott David E. , Vaala Sharon S. , Knigge Karl M. , Krobisch-Dudley Gerda
Published: December 2008

An in vitro assay for thyrotrophin releasing factor (TRF) is described which is based upon release of TSH from hemi-pituitary glands of normal rats. Pre-incubation of the pituitary gland in rat plasma results in considerable increase in sensitivity to approximately 35 pg of TRF. The content of TRF in median eminence of the hypothalamus of normal rats is estimated to be in the range of 102–140 pg. When median eminence is incubated in vitro with 3H-TRF or when radiolabelled hormone is infused intraventricularly, autoradiographic evidence indicates that the hormone is present in specialized ependyma (tanycytes) of the median eminence.
PURIFICATION AND PARTIAL CHEMICAL CHARACTERIZATION OF SHEEP NEUROPHYSIN
Authors: Chrétien Michel , Gilardeau Claude
Published: December 2008

A protein isolated from ovine pituitary glands has been purified, and its homogeneity assessed by NH2- and COOH-terminal amino acid determination, ultracentrifugation studies, and polyacrylamide gel electrophoresis after carboxymethylation. Its chemical and immunochemical properties are closely similar to those of beef and pork neurophysins, less similar to those of human neurophysins. It contains no tryptophan (like other neurophysins) or histidine (like all except bovine neurophysin-I and human neurophysins). It has alanine at the NH2-terminus and valine at the COOH-terminus. Its amino acid composition is similar to, but not identical with those of porcine and bovine neurophysins.
STUDIES ON THE MECHANISM OF IODINATION SUPPORTED BY THYROIDAL NADPH-CYTOCHROME c REDUCTASE
Authors: Hati Ratha N. , DeGroot Leslie J.
Published: December 2008

Further studies are reported on a tyrosine iodination system reconstructed from NADPH-cytochrome c reductase, either vitamin K3 or cytochrome c, and soluble iodinating enzyme from calf thyroid. K3Fe(CN)6, NADP+ and DCIP inhibited iodination. Iodination is also inhibited by addition of pyrogallol, o-dianisidine and guaiacol, possibly due to competition for H2O2. Haematin can replace cytochrome c in the iodinating system, but haematoporphyrin,haemoglobin, FeCl3 and K3Fe(CN)6 cannot. Trypsin-digested cytochrome c is not able to support the iodination, but boiled or dialyzed cytochrome c is as effective as native cytochrome c. The haematin response is not altered by trypsin treatment, boiling or dialysis. 14C-formate is oxidized to [14C]O2 in the presence of NADPH-cytochrome c reductase and cytochrome c or hematin.

From these data, it seems that NADPH, NADPH-cytochrome c reductase, and a third factor (vitamin K3, cytochrome c or haematin) possibly function as an H2O2 generating source to carry out the iodination reaction. It is suggested that a superoxide radical may be involved in the reaction and that the "third factor" serves to accelerate dismutation of the radical to H2O2.
THE SIMULTANEOUS ASSAY OF CORTISOL AND 17α-HYDROXYPROGESTERONE IN THE PLASMA OF PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA
Authors: Pham-Huu-Trung M. T. , Gourmelen M. , Girard F. , Marrec D.
Published: December 2008

The simultaneous determination of cortisol and 17α-hydroxyprogesterone (17-OHP) was carried out on a single plasma sample (0.6 ml) by the competitive protein-binding technique after a steroid partition by water and carbon tetrachloride.

This procedure was tested for sensitivity, accuracy, reproducibility and specificity. It was then applied to plasma samples obtained from 20 control subjects and 28 patients with 21-hydroxylase deficiency.

The cortisol value in the control group was 9.3 μg/100 ml ± 0.7 (se). This was moderately decreased in the untreated patients (group I): 6.7 μg/100 ml ± 0.9 (se), markedly decreased in those who discontinued treatment for 3 to 15 days (group II): 1.5 μg/100 ml ± 0.3 (se) and was suppressed in the treated patients (group III).

In normal children, the 17-OHP level was at the limit of sensitivity of the method. It was increased to 29 μg/100 ml ± 2.8 (se) in group I and was unchanged in group II: 26.5 μg/100 ml ± 3.4 (se). The plasma 17-OHP remained elevated in the patients who received an oral cortisol dose ≦ 20 mg/m2/ day and decreased to ≦ 3 μg/100 ml in those who were treated with a cortisol dose > 20 μg/m2/day.

A 17-OHP response to ® and a 17-OHP diurnal rhythm were were observed in the untreated patients. In contrast, the patients who had temporarily stopped their treatment had no reaction.

A negative correlation between the cortisol and ACTH levels appeared in groups I and II (N = 19; r = –0.66; P < 0.01) and a positive correlation was noted between the 17-OHP and urinary pregnanetriol values in all the patients (N = 33; r = 0.52; P < 0.01).

The reported technique described is simple and contributes to the diagnosis of congenital adrenal hyperplasia; it can also be useful in the follow-up of treated patients.
OESTROGENIC AND ANTIFERTILITY EFFECTS OF CHALCONE DERIVATIVES
Authors: Jacob Dennis , Kaul D. K.
Published: December 2008

Three newly synthesized non-steroidal derivatives of chalcone (benzalacetophenone), viz., 2′-chloro-4:4′-difluorochalcone (CH-4), 2′-chloro-3:4-methylenedioxy-4′-fluorochalcone (CH-6) and 2′-hydroxy-3:4-methylenedioxy-4′-fluorochalcone (CH-8) were evaluated for their oestrogenicity in the mouse and were found to possess a statistically highly significant (P < 0.001) uterotrophic effect at a dose of 1.0 mg/mouse. Of the three compounds CH-6 was the most potent. In comparison with oestradiol-17β, CH-6 proved to have a very low oestrogenic activity; however, it caused a highly significant increase in the mouse uterine weight at a dose of 0.1 mg/mouse, while a maximal effect was produced at a dose of 1.0 mg/mouse.

CH-6 was investigated for its post-coital antifertility effect in the mouse. At a dose of 1.0 mg/mouse and with the experimental regimen used CH-6 inhibited implantation in the mouse. When CH-6 was administered to 30-day old male mice for 5 consecutive days doses of 0.5 mg, 1.0 mg and 2.0 mg/mouse caused a highly significant decrease in the weight and size of the testes and seminal vesicles.