bluuebunny/crossref_metadata_2025 huggingface dataset:
OESTRIOL CONJUGATES IN AMNIOTIC FLUID. QUALITATIVE AND QUANTITATIVE ASPECTS, INCLUDING PRELIMINARY STUDIES IN Rh ISOIMMUNIZATION
Authors: Tikkanen M. J. , Adlercreutz H.
Published: December 2008

In addition to oestriol-16-glucosiduronate (OE3-16Gl), oestriol-3-sulphate (OE3-3S) and oestriol-3-sulphate, 16-glucosiduronate (OE3-3S,16Gl), a fourth conjugate, oestriol-3-glucosiduronate (OE3-3Gl), was tentatively identified in human late pregnancy amniotic fluid. A method was developed for the determination of all four conjugates in amniotic fluid and analyses were carried out on 11 normal samples and on six samples obtained in pregnancies complicated by mild Rh isoimmunization. The concentrations and proportions of these oestriol conjugates in normal amniotic fluid were: OE3-16Gl: 847 μg/l (61 %), OE3-3S: 245 μg/l (16%), OE3-3S,16Gl: 195 μg/l (14%) and OE3-3Gl: 134 μg/l (9%). In mild Rh isoimmunization the pattern of oestriol conjugates did not differ significantly from normal.
THE 5β-METABOLITES OF TESTOSTERONE: MODE AND SEX-SPECIFICITY OF THEIR FORMATION IN THE RAT LIVER
Authors: Ghraf Rüdiger , Hoff Hanns-Georg , Lax Edmund Rodney , Schriefers Herbert
Published: December 2008

Rat liver slices provide a suitable test model which, with simple and variable experimental conditions, contributes direct evidence for the formation of the 5β-metabolites, 17β-hydroxy-5β-androstan-3-one, 5β-androstane-3α,17β-diol and 3α-hydroxy-5β-androstan-17-one, from a direct hydrogenation of testosterone glucuronide.

When liver slices are incubated with testosterone in a KHR-phosphate medium no glucuronidation occurs and no 5β-metabolites are formed. They are produced, however, in a KHR-hydrogencarbonate medium, in which the slices are able to form glucuronides.

Moreover, the production rate of 5β-hydrogenated products like that of testosterone glucuronide formation is sex-specific. The male animal metabolizes less testosterone by oxidoreductive pathways than the female and thus exhibits the higher testosterone glucuronide formation. This higher glucuronide formation rate is closely associated with the appearance of 5β-metabolites in the aglucone fraction. Apparently, the testosterone glucuronide formation rate of the female animal is not sufficiently high to allow the production of 5β-configurated C19O2-aglucones in measurable quantities.

An experimentally induced feminization of the hepatic metabolism of genetically male rats by a single injection of 300 μg oestradiol benzoate on day 2 of life reduces the testosterone glucuronide formation rate to the female level and causes the 5β-metabolites to disappear.

Thus, it is evident that at least those 5β-metabolites mentioned above are products of a direct hydrogenation of testosterone glucuronide.
METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUE OF MALE RATS
Authors: Schmidt H. , Giba-Tziampiri O. , Rotteck G. v. , Voigt K. D.
Published: December 2008

The effects of 5α-androstane-3,17-dione2), of 5α-androstane-3β,17β-diol and of 5α-androstane-3α,17β-diol on protein and nucleic acid content as well as on the activities of some enzymes have been studied in the ventral prostate and the seminal vesicles of immature castrated rats. The androgens were administered in doses of 0.1 mg or 1 mg three times at 24 h intervals respectively, and the animals were sacrificed 24 h after the last injection. In accordance with the literature 5α-androstane-3,17-dione had a distinctly greater effect on the ventral prostates than on the seminal vesicles. Furthermore it could be demonstrated that in seminal vesicles this androgen had no effect on cell proliferation, whereas cell metabolism was slightly stimulated. The lack of cell proliferation in seminal vesicles is probably due to a smaller conversion of the steroid to 5α-dihydrotestosterone, i.e. to a weaker activity of the 17β-oxidoreductase in this target organ. The 5α-androstane-3β,17β-diol as well as the 5α-androstane-3α,17β-diol had a marked effect on DNA increase, comparable to that of 5α-dihydrotestosterone in both target organs. In the case of the 5α-androstane-3α,17β-diol this effect could be due to its high conversion rate to 5α-dihydrotestosterone. However, this is not the case for the 5α-androstane-3β,17β-diol. It seems possible that the 3β-hydroxy group of an androgen also exerts a cell proliferative effect. Concerning stimulation of cell metabolism in both target organs a greater effect was found after the administration of 5α-androstane-3α,17β-diol. This again leads to the conclusion that there are different sites of androgen action at the cellular level.
REGULATION OF RAT PITUITARY THYMIDINE KINASE ACTIVITY BY ANDROGENS
Authors: Valotaire Yves , Duval Jacques
Published: December 2008

Thymidine kinase (EC 2.7.1.21) has been studied in the pituitary postmitochondrial supernatant of growing male rats. This enzyme requires ATP and Mg++ to exhibit full activity. Pre-incubation at 37°C in the absence of substrate partly inactivates the enzyme. Apparent Michaelis constant (Km) is 5 × 10−6 m for normal rats as well as for castrated rats. After an initial decrease which terminates a few days after weaning, the specific activity is at a maximum between 30 and 35 days and then decreases regularly. These variations, previously observed for thymidine monophosphate kinase (dTMP kinase), confirm the importance of the prepuberal period in pituitary development.

Two days after castration of immature male rats, pituitary thymidine kinase specific activity increases 20 to 100 % over the control value. The injection of testosterone propionate or dihydrotestosterone to castrated animals maintains the activity to the basal level of the sham operated animals. Cycloheximide injected immediately after gonadectomy prevents the usual increase; low doses of actinomycin D do not abolish the difference between control and castrated animals.

If thymidine kinase is an enzyme involved in the regulation of DNA metabolism, it follows that androgens somehow exert a regulatory effect on pituitary development via the thymidylic nucleotides pathway. This effect might be due to dihydrotestosterone and might take place at the level of enzyme biosynthesis.
ANALYSIS OF THE INHIBITION OF THE ACTH RELEASE BY HYPOTHALAMIC IMPLANTS OF ATROPINE
Authors: Kaplanski J. , Smelik P. G.
Published: December 2008

The effect of anterior hypothalamic atropine implants on the secretion of corticotrophin in the rat, as indicated by the corticosteroid production by adrenal glands incubated in vitro and/or by the plasma corticosterone concentration, was studied. It was found that atropine implants markedly inhibit the adrenocortical responses evoked by all the stress stimuli tested, except for that to a CRF preparation. The onset of the blockade was very fast; the duration of the inhibition lasted for about 2 h. Smaller amounts of atropine (2×15 μg) were also effective when implanted bilaterally into the anterior hypothalamic region. It is concluded that cholinergic synapses in the hypothalamus may be involved in the activation of the pituitary-adrenal system after stressful stimuli.
ACUTE EFFECTS OF LITHIUM ON THE ACTION AND RELEASE OF ANTIDIURETIC HORMONE IN RATS
Authors: Torp-Pedersen Chr. , Thorn N. A.
Published: December 2008

Intravenous infusion of lithium in a concentration of 13 or 5 mm in a hypotonic fluid at a rate of 0.167 ml per minute to Inactin® anaesthetized 200 g rats caused an inhibition of the effect of 80 μU arginine-vasopressin on diuresis, urine osmolality and urine conductivity. This inhibition was not reversible for up to 150 min after cessation of the infusion of lithium.

When isolated hemilobes of neurohypophyses of rats were stimulated by a high concentration of potassium in the incubation medium, pre-incubation with 24 mm lithium in the medium did not inhibit the release of hormone. On the contrary, when the hemilobes were stimulated a second time, a higher release of hormone into the medium than in control experiments was found.
THYROID NODULE AUTONOMY: ITS DEMONSTRATION BY THE THYROTROPHIN RELEASING HORMONE (TRH) STIMULATION TEST
Authors: Karlberg Bengt E.
Published: December 2008

The response of thyrotrophin (TSH) to a single iv stimulation test with synthetic thyrotrophin releasing hormone (TRH) was compared with a thyroxine (T4)suppression test including thyroid scintiscans in 23 patients with palpable single thyroid nodules and in a control group of subjects without thyroid disease. In 16 patients with toxic adenomas and clinical hyperthyroidism no TSH-response to TRH was found as well as lack of suppression of the radioiodine uptake after T4. Thyroid scintiscans remained unchanged. Seven patients, judged to be euthyroid by clinical examination and laboratory tests, also showed no suppression by T4, as well as unchanged scintiscans. Six out of these seven patients had an absent TSH response to TRH, one had a "blunted" response. These patients were classified as having autonomously functioning thyroid adenomas. Thus there was a close correlation between absent TSH-response to TRH and non-suppressibility by T4 and it is concluded that in patients with single thyroid nodules, autonomous thyroid function can be demonstrated by the simple iv TRH stimulation test (potential hyperthyroidism or preclinical hyperthyroidism).

The possibility of an altered T3/T4-secretion ratio in the development of abnormal thyroid function in thyroid adenomas is discussed. It is suggested that the rapid iv TRH stimulation test is preferable to suppression tests as a screening test for the assessment of abnormal thyroid function in patients with single thyroid nodules, providing that a reliable TSH assay method is available.
LACTATION AND INTRA-MAMMARY PRESSURE IN RATS BEARING OESTROGEN, PROGESTERONE OR NORETHINDRONE MAMMARY IMPLANTS; EFFECTS OF OXYTOCIN
Authors: Bruce J. D. , Cofre X. , Ramirez V. D.
Published: December 2008

A study was made of the effect on lactation of progesterone, oestrogen or norehindrone implanted directly into the mammary gland of lactating rats compared to that in control animals. The results showed that progesterone did not disturb the milk yield of the mothers, growth of the pups or the action of oxytocin upon intra-mammary pressure. On the contrary, confirming earlier results, oestrogen showed a definitive deleterious effect upon lactation probably through an alteration of the milk ejection mechanism, since oestrogen reduced the mammary pressure effect of oxytocin. Norethindrone, a weak oestrogenic progestational compound, also showed an inhibitory action on lactation. These results support the hypothesis that oestrogen and progesterone have different direct actions upon the mammary function during lactation.
EARLY INSULIN RESPONSE TO GLUCOSE STIMULATION IN SIBLINGS OF JUVENILE DIABETICS
Authors: Sterky Göran , Thorell Jan I.
Published: December 2008

An intravenous glucose tolerance test was carried out in 33 young sibs of juvenile diabetics and in 53 matched controls. No significant difference was found in blood glucose, glucose disappearance rate or FFA response between the two groups. The variation of the early insulin response (ER) was wide, but the mean (±sd) was significantly lower for the sibs (71 ±41 μU/ml) than for the controls (116 ± 58 μU/ml). This difference was due mainly to the fact that high ER was almost lacking among the sibs, while low or medium ER occurred in both groups. No correlation was found between ER and age (12–26 years), body weight or skinfold thickness. The ER and the glucose disapperance rates were positively correlated. The healthy brother and sister, respectively, in two pairs of monozygotic twins, whose sibs had juvenile diabetes, showed normal glucose tolerance and a normal ER (58 and 103 μU/ml) falling within 1 sd of the normals.

The results lend support to the view that the ER is affected by close kinship to juvenile diabetics, revealed by group comparison. The results do not indicate that individual »pre-diabetics« can be identified by a low ER.
EFFECT OF PROGESTERONE ON RNA AND PROTEIN SYNTHESIS IN THE RAT UTERUS
Authors: Trams G. , Brewitt H. , Möllmann H. , Maass H.
Published: December 2008

The effect of gestagenic compounds on the oestrogen induced nucleic acid and protein synthesis of the rat uterus after castration was investigated. Progesterone causes an inhibition of 3H-uridine incorporation into uterine RNA. The inhibitory effect is strongest when progesterone is administered within 1 hour before isotope labelling. Evaluation of the free labelled nucleotides shows that this effect is not achieved by a blockade of permeability at the cell membrane or by reduction of the phosphorylation process. As a result of this progesterone-induced inhibition, protein synthesis is also reduced.

These results are discussed with regard to the modifying effect of progesterone on oestrogen dependent functions in the uterus.
SERUM LH DURING OVULATORY AND ANOVULATORY MENSTRUAL CYCLES IN MACAQUES
Authors: Mori J. , Hafez E. S. E. , Jaszczak S. , Kanagawa H.
Published: December 2008

Serum LH concentration was measured by radioimmunoassay, in peripheral blood obtained daily throughout 21 ovulatory and 3 anovulatory cycles in 18 crab-eating macaques (M. fascicularis) and 7 cycles in 4 bonnet macaques (M. radiata). The occurrence of ovulation was determined by laparoscopic and/or laparotomic examinations in both macaque species. A single mid-cycle peak in LH concentration was detected. LH concentrations were similar during the follicular and luteal phase of the cycle and increased abruptly to approximately a 2–10 fold rise at mid-cycle. LH surge occurred predominantly as a single distinctive peak lasting for one day. In some cycles additional burst in LH concentration occurred 2–4 days after the main LH peak. Ovulation occurred about 6–24 hours after the peak concentration of serum LH. At the time of LH surge, the cervical mucus showed maximal quantity, spinnbarkeit and arborization. The pre-ovulatory LH surge occurred most frequently on Days 10–13 of the cycle. The variability of the length of the menstrual cycle was due primarily to variation in duration of follicular phase, whereas the luteal phase was remarkably constant.

Anovulatory cycles were unaccompanied by mid-cycle LH surge. The mean value of serum LH concentration in anovulatory cycles was similar to the pre- and post-peak serum LH levels in ovulatory cycles. Serum LH was seldom flat but there were often rhythmic oscillations ranging from 20 to 100% of calculated mean value of serum LH.
DEHYDROGENASES IN THE PREPUBERTAL RAT OVARY: A HISTOCHEMICAL STUDY OF Δ5-3β-HYDROXYSTEROID DEHYDROGENASE AND ENZYMES OF CARBOHYDRATE OXIDATION FOLLOWING OXYTHIAMINE TREATMENT
Authors: Gupta Jayasree Sen , Dey Sudhansu K. , Deb C.
Published: December 2008

A histochemical study of the NAD- and NADP-linked dehydrogenases, Δ5-3β-hydroxysteroid dehydrogenase (Δ5-3β-ODH) and glucose-6-phosphate dehydrogenase (G-6-PD), and the corresponding tetrazolium reductases in prepubertal rat ovaries following the administration of oxythiamine HCl revealed diminution in the activities of the two dehydrogenases, while the NAD- and NADP-tetrazolium reductase activities remained unchanged. The same treatment resulted in stimulation of dihydrolipoic dehydrogenase (DLDH) and succinic dehydrogenase (SDH) activities in the ovarian tissues. Supplementary histochemical demonstration of Δ5-3β-OHD activity in phosphate buffer at pH 9.0 revealed a similar localization of the enzyme as that observed at pH 7.1 and which was free of the NAD-linked diaphorase activity. A diminution of this ovarian enzyme activity at this pH was also evident, following oxythiamine treatment. The results indicate a suppression of ovarian steroidogenesis in the prepubertal rats as a result of an alteration of the pentose phosphate pathway enzyme, G-6-PD, following treatment with oxythiamine HCl.
A SIMPLE CLINICAL TEST FOR MEASURING THE SERUM TESTOSTERONE RESPONSE TO INTRAVENOUS INFUSION OF HUMAN CHORIONIC GONADOTROPHIN (HCG)
Authors: Vivanco F. , Gonzalez-Gancedo P. , Ramos F.
Published: December 2008

A simple clinical test for measuring the blood testosterone response to intravenous infusions of HCG is described. Testosterone was measured in serum by a competitive protein-binding method at 0, 4, 12 and 24 h after the iv infusion of 5000 IU of HCG. Normal men showed a maximal increase of serum testosterone of about 2.5 times the basal levels at 12–24 h after starting the HCG infusion. Normal women did not respond at all to HCG stimulation. Four cases of proven Klinefelter syndrome (XXY) had basal testosterone values higher than in women but significantly lower than in normal men and did not show any response to HCG stimulation. In two orchidectomized patients with very low basal levels of serum testosterone the response to iv HCG was also negative. The test appears to measure specifically the testosterone secretion of the Leydig cells and may be very useful for the differential diagnosis of male hypogonadal syndromes.
EFFECT OF DOSE AND ADMINISTRATION PERIOD OF GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT
Authors: Thorngren K.-G. , Hansson L. I. , Menander-Sellman K. , Stenström A.
Published: December 2008

The effect of bovine growth hormone (NIH-GH-B15) on the growth in length of the proximal growth plate of the tibia in hypophysectomized female Sprague-Dawley rats was studied by the tetracycline method. The width of the growth plate was also determined and the weight of the body and heart was registered. The completeness of the hypophysectomy was determined microscopically.

The daily sc injection of 25 μg NIH-GH-B15 for 10, 20 or 30 days resulted in an increasing growth in length with increasing administration period. When various doses (5, 25, 100 or 400 μg) NIH-GH-B15 were administered daily for 20 days, the growth in length increased with the dose. A single injection of 45 mg/kg cortisone acetate given at hypophysectomy depressed the growth stimulation of growth hormone. The age at hypophysectomy also influenced the growth hormone-induced growth stimulation. Animals hypophysectomized at 40 days of age had a higher growth in length for the same doses and administration periods of growth hormone than those operated at 60 days of age. The width of the growth plate of the proximal tibia and the weight of the body and heart responded in a similar manner as the longitudinal bone growth to various doses and administration periods of growth hormone, but the changes were less obvious.

The dose-response relation after the administration of various doses of growth hormone for 20 days was tested for different growth parameters by the index of precision (λ). Of the growth parameters in this investigation, the accumulated growth in length in animals hypophysectomized at 60 days of age without cortisone at operation was found to be most suitable for dose-response determination of growth hormone. The intention is to develop a bio-assay for growth hormone.
BIOLOGICAL ACTIVITY OF CORTICOTROPHIN PEPTIDES WITH HOMO-ARGININE, LYSINE OR ORNITHINE SUBSTITUTED FOR ARGININE IN POSITION 8
Authors: Tesser Godefridus I. , Maier René , Schenkel-Hullinger Lotte , Barthe Pierre L. , Kamber Bruno , Rittel Werner
Published: December 2008

The steroidogenic and lipolytic activities of corticotrophin-(1–24)-tetracosapeptide and [Lys17,18]corticotrophin-(1-18)-octadecapeptide amide were compared with those of the corresponding analogues variously substituted in position 8 with homo-arginine, ornithine or lysine. Peptides substituted with homo-arginine showed a surprisingly high degree of biological activity; in all the tests performed, the loss of activity due to the substitution did not exceed a factor of 3 to 10, while peptides substituted with ornithine or lysine in position 8 only showed residual biological activity or none at all, depending on the test system used. The results reported demonstrated that the presence of a guanidino group (arginine or homo-arginine side chain) in position 8 of the ACTH peptide is essential for the preservation of a high level of biological activity; the length of the aliphatic chain carrying the guanidino group is of minor importance.
A COMPARISON OF THREE METHODS OF MEASURING TESTOSTERONE IN PLASMA: COMPETITIVE PROTEIN BINDING, RADIOIMMUNOASSAY WITHOUT CHROMATOGRAPHY AND RADIOIMMUNOASSAY INCLUDING THIN LAYER CHROMATOGRAPHY
Authors: Pirke K. M.
Published: December 2008

Three methods of measuring testosterone in male plasma were compared: A competitive protein binding technique using testosterone binding globulin, a radioimmunoassay including thin layer chromatography and a radioimmunoassay without chromatography. The antiserum obtained by immunization of rabbits with testosterone-3-(O-carboxymethyl)oximebovine-serum-albumin was characterized by its titer, affinity and specificity. The reliability criteria of the three methods were compared. Reagent blanks and the limit of detection were about 10 times higher in the competitive protein binding method than in the radioimmunoassay. The testosterone concentrations determined by the radioimmunoassay including chromatography and by the competitive protein binding method were in good agreement (y = 1.01 x, r = 0.96). There was a good agreement between the radioimmunoassay techniques (y = 1.05 x, r = 0.96). The results of the radioimmunoassay without chromatography were on an average 6.5 % higher than those of the radioimmunoassay including chromatography. The radioimmunoassay without chromatography is considered to be a reliable and practical routine method of measuring testosterone in male plasma. Normal values of 51 males ranged from 315 to 965 ng/100 ml (95 percentiles) with a median of 545 ng/100 ml.
SERUM THYROTROPHIN AND CIRCULATING THYROGLOBULIN ANTIBODIES IN SUBJECTS WITH NON-TOXIC GOITRE AND IN EUTHYROID SUBJECTS WHO HAD UNDERGONE SUBTOTAL THYROIDECTOMY OR RADIOIODINE THERAPY
Authors: Gordin Ariel
Published: December 2008

As part of a multiphasic health examination in two regions in the east of Finland, 5492 adult subjects were studied in the province of Kainuu and 2767 in the city of Joensuu. The general prevalence of goitre was 6.0 % in the Kainuu region and 4.2 % in Joensuu and that of frank hypothyroidism 0.3 and 0.4 %, respectively. The serum thyrotrophin (TSH) and circulating thyroglobulin antibodies (TgA) were determined in subjects with non-toxic goitre, in euthyroid subjects who had undergone thyroidectomy or radioiodine therapy, and in matched controls without thyroid disease.

In a group of 99 subjects with non-toxic goitre the mean serum TSH (2.9 μU/ml) did not differ from the mean (2.9 μU/ml) of the 40 corresponding controls. Of the 36 subjects who were euthyroid after thyroidectomy without recurrent goitre, 9 had an elevated serum TSH level, and the mean value for this group (5.8 μU/ml) was significantly higher than the mean (3.5 μU/ml) for the 36 controls. Of the 19 subjects with recurrent non-toxic goitre, 2 had an elevated serum TSH level, but the mean value (5.0 μU/ml) was not significantly higher than the mean (3.4 μU/ml) for the 19 controls. Of the 15 subjects who were euthyroid after radioiodine therapy, 4 had an elevated serum TSH level, and the mean value (6.2 μU/ml) was significantly higher than the mean of the 15 controls (3.3 μU/ml).

The subjects with non-toxic goitre and positive TgA titres had a significantly higher mean serum TSH than those with goitre but negative TgA titres (3.8 against 2.7 μU/ml). The thyroidectomized subjects without recurrent goitre who had detectable TgA had a significantly lower mean serum TSH than the corresponding subjects who were TgA-negative (4.0 against 6.4 μU/ml). The subjects with recurrent goitre and positive TgA titres had a higher mean TSH level than those without TgA (7.6 against 3.5 μU/ml). but the difference was not significant. Subjects previously treated with radioiodine who had positive TgA titres had a lower mean serum TSH than those who were TgA-negative (4.6 against 6.8 μU/ml), but the difference was not significant.

About a fourth of the subjects who were euthyroid after previous thyroidectomy or radioiodine therapy in the present study had elevated serum TSH values, indicating slight thyroid failure.

The present results also indicate that auto-immune phenomena may play some part in producing slight thyroid failure in non-toxic goitre, but that other factors are responsible for the elevated TSH values in euthyroid subjects after thyroidectomy or treatment with radioiodine.
"IN VIVO RADIOIMMUNOASSAY" OF ALDOSTERONE
Authors: Vecsei P. , Gless K. H. , Winter M. , Hanka-Postozky M.
Published: December 2008

Aldosterone antibodies were raised in sheep immunized with a complex of D-aldosterone-21-hemisuccinate and bovine serum albumin. The intravenous injection of these antibodies into rats caused a delay in the disappearance rate of tritiated aldosterone from the blood. The degree of this effect depends on the body weight of the animals, on the amount of the antiserum given, and on the interval between the injection of antibodies and that of labelled aldosterone.

After the injection of aldosterone antibodies and the tritiated hormone, the plasma concentration of labelled aldosterone was related to the rate of secretion of the hormone. When aldosterone secretion was low, subsequent to high sodium intake, or abolished after adrenalectomy, the plasma concentration of tritiated aldosterone was higher than in the control rats. Stimulation of aldosterone secretion by furosemide or ACTH, or administration of cold aldosterone resulted in a decrease in the plasma concentration of the labelled hormone. It is suggested that the relationship between the amount of free aldosterone in the "inner pool" and the plasma concentration of tritiated aldosterone is the consequence of a competition of labelled and unlabelled hormone for the binding capacity of the antibody.
PERIPHERAL PLASMA LEVELS OF OESTROGEN AND PROGESTERONE IN PREGNANT RHESUS MONKEYS TREATED WITH DEXAMETHASONE
Authors: Bosu William T. K. , Johansson Elof D. B. , Gemzell Carl
Published: December 2008

The effect of dexamethasone1) on the peripheral plasma levels of the sex steroids was investigated in four pregnant monkeys during six treatments at the end of the second and third trimesters. A daily dose of 10 mg dexamethasone was administered intramuscularly into each pregnant monkey for three days. All the treated monkeys delivered normal healthy babies within the expected time of parturition.

A decrease in oestrogens and an increase in progesterone in the peripheral blood plasma were observed during the dexamethasone treatment. The increase in the peripheral plasma levels of progesterone observed was greater in the monkeys treated at the end of the second trimester. The peripheral plasma levels of 17α-hydroxyprogesterone were very low and showed no change in any of the pregnant monkeys treated with dexamethasone.
EFFECTS OF TESTOSTERONE AND 5α-DIHYDROTESTOSTERONE ON WEIGHT GAIN AND 3H-THYMIDINE INCORPORATION IN ACCESSORY SEX GLANDS OF CASTRATED MALE RATS
Authors: Tuohimaa P. , Oksanen A. , Niemi M.
Published: December 2008

Albino male rats were injected subcutaneously (sc) one month after castration with 1 mg of testosterone (T) or dihydrotestosterone (DHT) daily for two weeks. Every twelve hours a pair of rats were injected iv with tritiated thymidine and killed one hour later. The first pair of rats were killed 7 h after the first hormone injection. The accessory sex organs were weighed and processed for radio-autography.

The weight response of the accessory sex organs was of the same magnitude after T and DHT. However, DHT was slightly more effective in inducing the growth of the seminal vesicle, the coagulating gland, the preputial gland and the epididymis. The organs reached a constant weight in about 8–10 days after the onset of the hormone treatment. The accessory sex organs could be divided into two groups on the basis of their weight response to DHT and T: 1) Highly responsive tissues (seminal vesicle, coagulating gland and prostate) showed a 5–8 fold increase in weight to 1 mg of DHT or T during stimulation over two weeks. 2) Less responsive tissues (epididymis and preputial gland) can only double their weights during the treatment.

By measuring the mitotic response to castration and to the administration of DHT or T the tissues could be categorized into two similar groups:

Seminal vesicle, coagulating gland and prostate are highly dependent on androgen supply, since their mitotic activity increases dramatically in 42–66 h after the initiation of hormone administration. This first DNA

synthetic peak is followed by irregular series of peaks of decreasing amplitude. In six days the fluctuation in the mitotic activity is stabilized to the level of the uncastrated control animals. In addition, these organs respond slightly more rapidly and more extensively to DHT than to T.

The epithelial cells of the preputial gland are less dependent on androgen supply. A significant degree of mitotic activity still persists after castration. The mitotic activity increases 18 h after androgen administration. Fluctuations of mitotic activity are retained during the entire two weeks' period.
A FAT-MOBILIZING FACTOR IN RAT SERUM
Authors: Curtis-Prior P. B. , Hanley T.
Published: December 2008

The serum of rats promoted triglyceride breakdown in isolated adipose tissue cells incubated in vitro, as shown by increased glycerol release into the medium. The serum of fed rats had a smaller fat-mobilizing action than that of rats fasted for 20 h. There was a very close linear relation of dose-response versus dose, as occurs in other physiological responses provoked by a hormone acting on a limited number of receptors. The maximum lipolytic effect of serum from fasted animals was of the same order as the maximum effect of noradrenaline, and amounted to a breakdown of about 1.5% of the adipose cell triglyceride per hour. The triglyceride breakdown provoked by serum was inhibited by the β-blocking drug propranolol, but was not affected by insulin even in high concentration.
SELF-LIMITING EPISODES OF JODBASEDOW
Authors: Nilsson Göran
Published: December 2008

Four patients with Jodbasedow (iodine-induced hyperthyroidism), who experienced a spontaneous remission of thyrotoxicosis within a few months without specific antithyroid treatment are described. All the patients lived in a non-endemic area and had a nodular goitre. All of them gave a story of administration of iodine-rich compounds such as contrast medium for cholecystography or iodine-containing exceptorants, just before the appearance of thyrotoxic symptoms. The rapid improvement of hyperthyroid symptoms after avoiding excessive iodine administration strengthens the causal relationship in Jodbasedow. Though a definitive statement on the best treatment of this disease must await further studies. the present report provides some reason for believing that Jodbasedow is a benign type of thyrotoxicosis, which responds well to conservative treatment without ablation by surgery or radioiodine. Furthermore, the present findings emphasize previous warnings against the administration of unphysiologically large amount of iodine to euthyroid goitre patients because of the risk of precipitating thyroid dysfunction.
COMPLEX ANTITHYROID PROPERTIES OF THE LITHIUM ION
Authors: Männistö P. T. , Leppäluoto J. , Virkkunen P.
Published: December 2008

Acute effects of lithium chloride (LiCl, 5 mEq./kg × 3), rubidium chloride (RbCl, 5mEq./kg×3), carbimazole (0.05 mEq./kg × 3) and short-term transfer stress on thyroid iodine metabolism were studied in rats fed a normal-iodine diet (NID). In addition, the effect of graded doses of LiCl (0–7.5 mEq./kg × 3) was studied in rats fed a low-iodine diet (LID).

In the animals on NID carbimazole, LiCl and RbCl decreased the 4 h uptake of 131I. In chromatography it was found that only carbimazole and LiCl significantly decreased the synthesis of T3 + T4. Plasma TSH (radioimmunoassay) levels were slightly decreased by short-term transfer stress, RbCl and LiCl, but increased by carbimazole.

In the animals on LID, the 131I uptake at 4 h decreased and correspondingly the plasma radioactivity increased with increasing doses and plasma concentrations of Li+. In chromatography the relative amounts of iodothyronines and DIT decreased, that of MIT increased, and the percentage of iodide remained unchanged. With a minimal effective dose, Li reduced only T4 and T3, with the higher dose DIT, then iodide and the total uptake of 131I, and lastly MIT. The plasma corticosterone level tended to increase and TSH level to decrease as the plasma Li concentration increased.

Thus lithium in massive doses seems to be an antithyroid agent, its effects on thyroidal uptake and distribution of 131I resembling that of very small doses of propylthiouracil. The inhibitory effects of Li are dose-dependent. The decrease in plasma thyroxine level probably initiates the series of events which may lead to hypothyroidism, goitre or both conditions.
A NEW PRINCIPLE FOR THE COMPARISON OF INSULIN SECRETORY RESPONSES
Authors: Johansen Klaus
Published: December 2008

In an attempt to circumvent the difficulties inherent in the use of insulin/glucose ratios a new principle for the comparison of insulin secretory resonses has been developed. From large groups of obese and non-obese people subjects are selected so that the subgroups ultimately formed are comparable with regard to age and to their degree of glucose tolerance. This means that the blood glucose curves of the two groups are merging and that the beta cells are subjected to identical glycaemic stimuli. The study shows that obese young non-diabetics and obese young and old diabetics exhibit an augmented insulin response to stimulation with oral and intravenous glucose and to intravenous tolbutamide. No increase in plasma insulin secretory response is, however, demonstrable in obese, old non-diabetics.
EFFECT OF BLOCKADE OF THE α-ADRENERGIC RECEPTORS ON INSULIN RESPONSE TO GLUCOSE INFUSION IN PREDIABETIC SUBJECTS
Authors: Efendić S. , Cerasi E. , Luft R.
Published: December 2008

The α-adrenergic blocking agent phentolamine significantly stimulates, but does not normalise glucose induced insulin release in prediabetic subjects. In earlier studies, under the same experimental conditions, no effect of the drug was observed in non-prediabetic subjects. The present data suggest that the diminished insulin response to glucose in prediabetics may partially be mediated by an enhanced responsiveness of the α-receptors of the pancreatic β-cells.
RADIOIMMUNOASSAY FOR ALDOSTERONE WITHOUT CHROMATOGRAPHY
Authors: Vetter Wilhelm , Vetter Hans , Siegenthaler Walter
Published: December 2008

A radioimmunoassay for the determination of urinary aldosterone-18-glucuronide has been developed for the clinical laboratory.

Ten ml of urine is pre-extracted with methylene chloride and then submitted to acid hydrolysis. This is followed by a second methylene chloride extraction. The aldosterone concentration in these extracts is determined with antisera obtained from rabbits immunized with an aldosterone-oxime bovine gamma globulin conjugate.

In view of the high recovery of [1,2-3H] aldosterone no internal indicator standards were used.

The sensitivity of the overall assay was 0.44 μg/24 h. The coefficient of variation was 3.7 % within a single assay and 13.6 % for multiple assays. The specificity of the method was examined by comparison with a double isotope dilution derivative method and by simultaneous use of 6 different antisera.

Under normal sodium intake the urinary excretion of the acid-labile aldosterone-18-glucuronide ranged from 4.0 to 13.0 μg/24 h in 9 normal male subjects.
IN VITRO METABOLISM OF [6,7-3H]NORETHYNODREL IN THE HUMAN ENDOMETRIUM AND THE MYOMETRIUM
Authors: Murugesan K. , Hingorani V. , Laumas K. R.
Published: December 2008

The human endometrium and the myometrium have the capacity to convert [6,7-3H]norethynodrel to norethindrone, 17α-ethynyl-3α,17β-dihydroxy-5-(10)-oestrene and two other unidentified metabolites. Under in vitro conditions, 80–90 % of 3H-norethynodrel was converted to its metabolites within 90 min. The metabolites formed were the same for both the endometrium and the myometrium. The amount of norethynodrel converted to its metabolites was more in the proliferative phase than in the secretory phase. Among the subcellular fractions of the myometrium, mitochondrial and microsomal fractions metabolised norethynodrel to norethindrone and two polar metabolites with low chromatographic mobility. In the myometrial 105 000 × g supernatant fraction, 17α-ethynyl-3α,17β-dihydroxy-5(10)-oestrene was formed in addition to norethindrone and the polar metabolites. The significance of the formation of norethindrone – a potent oral progestin as a product of the metabolism of norethynodrel and its possible action at the uterine level in the control of fertility is discussed.
THE DIAGNOSTIC AND PROGNOSTIC VALUE OF THE 20 min 99mTc-UPTAKE IN THE THYROID GLAND
Authors: Kirkegaard C. , Friis Th. , Hansen J. E. Mølholm , Siersbæk-Nielsen K.
Published: December 2008

The 20 min 99mTechnetium (99mTc) pertechnetate uptake in the thyroid gland has been investigated in 144 patients and compared with the 24 h 131I-uptake.

The diagnostic values in 39 patients with hyperthyroidism was found to be the same with both tests whereas the 24 h 131I-uptake gave a better discrimination between the controls and 13 hypothyroid patients than the 20 min 99mTc-uptake.

There was no significant difference in the prognostic value of T3 suppression of the 20 min 99mTc-uptake and the 24 h 131I-uptake in 31 patients receiving long-term antithyroid treatment.

The 20 min 99mTc-uptake offers several advantages as compared with the 131I-uptake especially a very low radiation dose and less time consumption.
PATTERNS OF CIRCULATING OESTRONE, OESTRADIOL-17β AND PROGESTERONE DURING PREGNANCY IN THE RHESUS MONKEY
Authors: Bosu William T. K. , Johansson Elof D. B. , Gemzell Carl
Published: December 2008

The maternal peripheral plasma levels of oestrone (E1)*, oestradiol-17β (E2) and progesterone (P) were determined by RIA during pregnancy in 8 rhesus monkeys (Macaca mulatta). Of special interest were the time courses and the inter-relationships of these steroids during the first month of pregnancy and during the pre- and post-parturient periods. A significant increase in the plasma levels of E1 and E2 occurred at the end of the fertile cycle and lasted for several days and again during the last week before parturition. The plasma levels of E1 and E2 fell dramatically after parturition and remained low during the immediate post-partum period. Two surges in the progesterone levels in plasma occurred at the end of the third week of the fertile cycle and between day 34 and 46 after the onset of menstruation. The progesterone levels in plasma during the remaining gestational period varied widely but a significant increase was found during the days before parturition. A decrease in the plasma levels of P was observed after parturition but the levels of P did not reach follicular phase levels during the post-partum period studied. The possibility of oestrogen secretion from follicles stimulated by chorionic gonadotrophins is discussed as well as the release of prostaglandins by oestrogen before parturition.
AGE RELATED CHANGES AND INTERRELATIONSHIPS BETWEEN PLASMA TESTOSTERONE, OESTRADIOL AND TESTOSTERONE-BINDING GLOBULIN IN NORMAL ADULT MALES
Authors: Pirke Karl M. , Doerr Peter
Published: December 2008

Testosterone (T), oestradiol-17β (Oe2) and binding capacity of the testosterone-binding globulin (TeBG) were measured in plasma of 84 adult males (22–90 years). The medians for age group I (22– 61 years, n = 50) were: T 545 ng/100 ml, Oe2 1.66 ng/100 ml, TeBG capacity 1.44 μg T/100 ml; the medians for age group II (67–90 years, n = 34) were: T 459 ng/100 ml, Oe2 2.56 ng/100 ml, TeBG capacity 2.05 μg T/100 ml. The decrease of T and the increase of Oe2 and TeBG capacity with age were significant. The significant correlation (P < 0.01) for either age group between T and Oe2 may be ascribed to a simultaneous secretion and/or a peripheral conversion of T to Oe2. The significant correlation (P < 0.05) between T and TeBG for the old age group probably reflects the comparatively high percentage of total plasma T bound to TeBG. The biological meaning of the correlation between Oe2 and TeBG is discussed.
EFFECT OF WITHDRAWAL OF GROWTH HORMONE ADMINISTRATION ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT
Authors: Thorngren K.-G. , Hansson L. I.
Published: December 2008

Bovine growth hormone was given daily for 10 days to female Sprague-Dawley rats hypophysectomized at the age of 60 days, beginning 15 days post-operatively. Longitudinal bone growth, studied in the proximal tibia, was reactivated and continued at an accelerating rate during the period of hormone administration and for a further 5 days after its withdrawal, but then ceased.

The effect of withdrawal of growth hormone on the width of the growth plate of proximal tibia, the size of its degenerative cells, and the weight of body and heart was also studied.

The cell production in the proximal growth plate of tibia was calculated. The changes in longitudinal bone growth were found to be due mainly to changes in cell production in the growth plate.
RADIOIMMUNOASSAY OF OESTRONE AND OESTRADIOL IN THE PERIPHERAL PLASMA OF THE DOMESTIC FOWL IN VARIOUS PHYSIOLOGICAL STATES AND OF HYPOPHYSECTOMIZED AND OVARIECTOMIZED FOWLS
Authors: Senior B. E.
Published: December 2008

A radioimmunoassay was developed to measure the levels of oestrone and oestradiol in 0.5–1.0 ml of domestic fowl peripheral plasma. The oestrogens were extracted with diethyl ether, chromatographed on columns of Sephadex LH-20 and assayed with an antiserum prepared against oestradiol-17β-succinyl-bovine serum albumin using a 17 h incubation at 4°C. The specificity, sensitivity, precision and accuracy of the assays were satisfactory. Oestrogen concentrations were determined in the plasma of birds in various reproductive states. In laying hens the ranges of oestrone and oestradiol were 12–190 pg/ml and 29–327 pg/ml respectively. Levels in immature birds, in adult cockerels and in an ovariectomized hen were barely detectable. The mean concentrations of oestrone and oestradiol in the plasma of four non-laying hens (55 pg/ml and 72 pg/ml respectively) and one partially ovariectomized hen (71 pg/ml and 134 pg/ml respectively) were well within the range for laying hens. It is evident that the large, yolk-filled follicles are not the only source of oestrogens in the chicken ovary.
AUGMENTATION OF THE RAT UTERINE WEIGHT RESPONSE TO HUMAN CHORIONIC GONADOTROPHIN BY VARIOUS STEROIDS
Authors: Hipkin L. J.
Published: December 2008

Dehydroepiandrosterone (DHA) augments the activity of human chorionic gonadotrophin (HCG) in the rat by increasing endogenous pituitary gonadotrophin secretion. The following experiments were undertaken to investigate the mechanism underlying this effect. Androstenedione (40 μg), dihydrotestosterone (200 μg) and testosterone (200 μg) augmented the rat uterine weight response to 0.5 IU of HCG. At these doses, the steroids did not affect basal uterine weight although this was increased when 1 mg of a steroid was injected. Androsterone (1 mg), 17α-hydroxypregnenolone (1 mg) and progesterone (200 μg) neither augmented HCG activity nor increased basal uterine weight. Ovarian weight differences were not significant in any of the experiments.

Androstenedione, DHA, dihydrotestosterone and testosterone (200 μg dose level) did not significantly affect the uterine weight of castrated animals, and responses to 0.04 μg of oestradiol were not potentiated.

The results with androstenedione, dihydrotestosterone and testosterone are identical to those obtained with DHA and suggest that these steroids may also increase pituitary gonadotrophin secretion.
POSSIBLE MODE OF ACTION OF CLOMIPHENE
Authors: Chatterjee Amar , Gupta Tarun , Sengupta Kamal
Published: December 2008

Clomiphene, a synthetic non-steroidal agent, when injected into rats at a dose level of 3.0 mg/kg b. w. on days 5, 7 and 9 of pseudopregnancy causes termination of decidual growth. Moreover, its administration on days 12, 14, 16 and 18 of pregnancy causes death and resorption of the foetuses leaving regressing placentae at the sites of their attachment in the uteri. Luteolysis and ovarian poly-follicular conditions were also evident in both instances. Concomitant administration of prolactin or progesterone along with the clomiphene consistently prevented the interruption of clomiphene-induced lysis of deciduoma, gestation and other associated ovarian abnormalities. It is suggested that the abnormal development of the follicular apparatus possibly caused by the clomipheneinduced endogenous FSH during pseudopregnancy or pregnancy is the most likely explanation for the termination of decidual growth or gestation in rats.
PLASMA TESTOSTERONE IN MALE PUBERTY
Authors: Knorr D. , Bidlingmaier F. , Butenandt O. , Fendel H. , Ehrt-Wehle R.
Published: December 2008

Plasma testosterone was investigated by gas-liquid chromatography with an electron capture detector in a cross-sectional study in childhood and during puberty in 214 boys. The testosterone values were correlated with sexual characteristics such as axillary hair, pubic hair, testicular size and bone age.

In 22 individuals during puberty a longitudinal study was started, indicating a very steep increase of plasma testosterone between 40 and 240 ng/100 ml. This stage is mostly passed through very rapidly within 10 months.

Plasma testosterone, growth velocity and weight gain were correlated in two boys during puberty. The peak of growth spurt occurs between 50 and 170 ng of plasma testosterone.
THE UPTAKE AND METABOLISM OF [4-14C]TESTOSTERONE IN HUMAN BREAST CANCER GROWN IN ORGAN CULTURE
Authors: Geier Avraham , Horn Hadassah , Lichtshtein Esther , Levij I. S. , Finkelstein Michael
Published: December 2008

The uptake and metabolism of [4-14C]testosterone was studied in 10 tissue samples of human female breast grown in organ culture. Four samples were from carcinomas, 4 were non-cancerous tissue from the uninvolved part of the cancer bearing breast, and two were from fibroadenomas. In all cases testosterone was metabolized to androstenedione, androsterone, dihydrotestosterone, androstanedione and androstanediol. The non-cancerous tissues showed greater retention, uptake and conversion of testosterone into metabolites than the cancerous tissues. The retention of testosterone in the fibroadenomas samples was lower than that in samples of either cancerous or non-cancerous tissue. The uptake and conversion of testosterone into metabolites in one case of fibroadenoma was similar to that seen in cancerous tissue samples but in the other case it was considerably higher.
PARTICIPATION OF HORMONE IN THE EARLY STAGES OF THE IMMUNE RESPONSE
Authors: Maor D. , Englander T. , Eylan E. , Alexander P.
Published: December 2008

Immunization of weanling rats with sheep erythrocytes leads within 24 hours to an increase in DNA synthesis in the spleen but not in the lymph nodes. Growth hormone, insulin and oestradiol, given together with the antigen, increase the response of the spleen to antigenic stimulation, and initiate a pronounced increase in DNA synthesis of the lymph nodes in response to antigen. On the other hand, thyrotrophin reduces the rate of DNA synthesis in spleen and in lymph nodes following antigenic stimulation. When administered singularly, only growth hormone and insulin increase DNA synthesis in spleen, but not in lymph nodes.

It is suggested that growth hormone, oestradiol, or insulin are involved in the proliferative response of lymphoid organs following an antigenic stimulation.