bluuebunny/crossref_metadata_2025 huggingface dataset:
INDUCTION OF OVULATION IN PROGESTIN-TREATED ADULT RATS
Authors: Banik U. K. , Haltrecht Irene , Herr F.
Published: December 2008

The ovulation was blocked in a strain of 4 day cyclic rats by a single intramuscular injection of different doses of medroxyprogesterone acetate (MPA). The MPA was given one day before the expected day of prooestrus. The ovulation-blocking effect of smaller doses of MPA (0.01 and 0.1 mg/rat) was reversed by two orally active oestrogens, namely, ethynyl oestradiol and a new oestrogen, AY-11,483. The anti-ovulatory effect of 1.0 mg MPA could not be reversed by smaller or bigger doses of any one of the oestrogens. These oestrogens were given orally also on the day before prooestrus. Evidence of ovulation was obtained by counting freshlyshed ova microscopically from the fallopian tubes on the expected day of the following oestrus. Both of these oestrogens were active in reversing the ovulation-blocking effect of smaller doses of MPA. It has been suggested that a bigger dose of MPA, in addition to blocking the release of pituitary-LH, also suppressed the ovarian response to exogenous gonadotrophin.
EFFECTS OF CONTINUOUS DAILY ADMINISTRATION OF 0.3 mg OF NOREHTINDRONE ON THE PLASMA LEVELS OF PROGESTERONE AND ON THE URINARY EXCRETION OF PREGNANEDIOL AND TOTAL OESTROGENS
Authors: Larsson-Cohn U. , Johansson E. D. B. , Gemzell C.
Published: December 2008

Daily determinations of the plasma level of progesterone and the urinary excretion of total oestrogens and pregnanediol were performed in 7 subjects during one control cycle, followed by three months of daily continuous treatment with 0.3 mg of norethindrone (NET).

The control cycles were ovulatory according to the parameters investigated. During treatment there was a tendency to cyclically increased oestrogen excretion, this being most marked in cycles with very depressed progesterone-pregnanediol levels.

All the subjects showed signs of cyclical luteal activity. In most cases, the levels of progesterone and pregnanediol were lower than during the corresponding control cycles. It is suggested that this might be due to deficient corpus luteum function.

The drug had no thermogenic effect. The length of the treatment cycles varied between 22 and 49 days. Only two of the women showed intermenstrual bleeding.

It seems that 0.3 mg of NET has a weaker effect on the hormone levels than 0.5 mg of NET, but a stronger effect than 0.5 mg of chlormadinone acetate.
TWO MODES OF INTERACTION BETWEEN OESTROGEN AND ANTI-OESTROGEN
Authors: Terenius Lars
Published: December 2008

A comparative investigation was carried out on the modes of action of anti-oestrogenic substances of different chemical structures and of different biological profiles. Most extensively investigated were mesobutoestrol and U-11100A. While meso-butoestrol is only antagonistic when applied locally to a target tissue, U-11100A is a systemic antagonist. The interactions of these compounds with tritium-labelled 17β-oestradiol were tested in vivo and in vitro on mouse uteri and vaginae and in vitro on an experimental rat mammary carcinoma.

It was found that meso-butoestrol had a very high competitive affinity for the oestrogen binding sites but that its action was easily reversible and particularly so on the vagina. Since it is not retained its antagonistic activity is only manifested biologically under special circumstances. U-11100A had a lower affinity for the binding sites but its blocking action was much less reversible. By combination with the binding sites to a stable complex of low intrinsic biological activity it prevents the full action of a »true« oestrogen.

The results illustrate the complexity in the interactions between oestrogens, anti-oestrogens and the target tissues. To characterize the actions of an anti-oestrogen, both affinity for the binding sites and ease of reversibility should be considered. Furthermore, binding characteristics of different target tissues are not necessarily similar.
RADIOIMMUNOASSAY OF ANGIOTENSIN II IN PLASMA
Authors: Sundsfjord Johan A.
Published: December 2008

Specific antibodies were produced in rabbits with val5angiotensin II amid (Hypertensin®, Ciba) attached to succinyl-poly-l-lysine. Hypertensin was labelled with iodine-125 (125I) according to a modified Hunter-Greenwood procedure. Ion exchange chromatography followed by antibody association-dissociation technique was used in the purification of the labelled hormone.

The separation between bound and free hormone was performed on Sephadex G-25. Maximum binding of the labelled material to the antibody was achieved within one hour. The equilibrium between bound and free hormone was markedly influenced by temperature.

It was found that Hypertensin and ileu5angiotensin II exhibited equal immunological activities, whereas ileu5angiotensin I displayed less than 1% of the affinity of angiotensin II towards the antibody.

For the determination of angiotensin II in plasma, samples were collected in chilled tubes containing EDTA and BAL at pH 5.5, in order to inhibit any possible enzymatic generation and degradation of angiotensin II. Concentration was achieved on a column of Dowex 50W – X2(NH4+) resin followed by freeze-drying of the eluate. Dilution of the material obtained behaved as standard angiotensin II in the assay.

The recovery of 0.5–10 ng of angiotensin II added to 10 ml of plasma was 85–111%. The normal range for young healthy adults was 2.7 ± 1.4 (sd) ng/100 ml, in agreement with reports by some other groups.
THE STAGE OF SPERMATOGENESIS INVOLVED IN THE TESTICULAR-HYPOPHYSEAL FEED-BACK MECHANISM IN MAN
Authors: Johnsen Svend G.
Published: December 2008

In 284 patients with a great variety of primary testicular disorders registration of spermatogenesis was performed with the testicular biopsy score count method described by the author. Correlation analyses between the score count steps and gonadotrophin excretion show a great rise when spermatozoa (late spermatids) disappear from the testis. There is a high correlation between the per cent of tubuli possessing spermatozoa and the gonadotrophin level. Disappearance also of spermatids or spermatocytes or spermatogonia induces no further rise in gonadotrophins and no separate effect of these cells on gonadotrophins could be demonstrated. Some influence upon the gonadotrophin level was found when only Sertoli cells were present but this was small as compared with the effect of spermatozoa.

It is concluded that the stage of spermatogenesis involved in the testicularhypophyseal feed-back mechanism in man is the last stage where the spermatozoon is finished and matured. The way this stage exerts its influence upon the gonadotrophin level is briefly discussed.
SUSTAINED RELEASE HORMONAL PREPARATIONS
Authors: Kincl Fred A. , Sundaram K. , Chang C. C. , Rudel Harry W.
Published: December 2008

Dissolution of progesterone, 19-nor-4-pregnene-3,20-dione and 6-methyl-17α-acetoxy-4,6-pregnadiene-3,20-dione was measured from lipid pellets of various composition. Values obtained in in vitro studies indicated that, after an initial period, the dissolution was constant. Studies in hamsters demonstrated that in vivo absorption declined with time at a rate similar to that observed with polydimethylsiloxane implants.
IDENTIFICATION AND DETERMINATION OF NEUTRAL STEROID SULPHATES IN HUMAN FOETAL ADRENAL AND LIVER TISSUE
Authors: Huhtaniemi I. , Luukkainen T. , Vihko R.
Published: December 2008

The endogenous neutral steroids in adrenal and liver tissue obtained from foetuses of 12–17 weeks gestation were investigated. After extractions, the steroids were fractionated into a monosulphate and a disulphate fraction on Sephadex LH-20. The conjugates were cleaved by solvolysis, and purified on silicic acid and their trimethyl silyl ethers were analysed by gas-liquid chromatography and gas chromatography-mass spectrometry. Only neutral steroid monosulphates were found. The following compounds were identified in the monosulphate fraction of adrenal tissue: dehydroepiandrosterone, 16α-hydroxydehydroepiandrosterone, pregnenolone and 17α-hydroxypregnenolone, and of liver tissue; dehydroepiandrosterone, 16α-hydroxydehydroepiandrosterone, androst-5-ene-3β,16α,17β-triol, pregnenolone, 17α-hydroxypregnenolone and 16α-hydroxypregnenolone. The identifications and the results of the quantitative determinations of endogenous neutral steroid sulphates suggest that pregnenolone is synthesised in vivo in the foetal adrenal and converted to 17α-hydroxypregnenolone and dehydroepiandrosterone sulphates. The latter compound is further transformed to 16α-hydroxydehydroepiandrosterone sulphate. No 16α-hydroxylation of pregnenolone was observed in adrenal tissue, whereas liver tissue seems to form 16α-hydroxypregnenolone. Reduction of a 17-keto group to 17β-hydroxyl and a 20-keto group to 20α-hydroxyl seems to take place in liver but not in adrenal tissue.
FOLLICLE KINETICS IN THE OVARY OF THE CYCLIC MOUSE
Authors: Pedersen Torben
Published: December 2008

The variations in size, numbers and growth rates of mouse ovarian follicles were investigated at different stages of the oestrous cycle. Autoradiographs were prepared of sections of ovaries after pulse-labelling with tritiated thymidine. By determining the growth rate of the granulosa cells expressed as their doubling times, it was possible to estimate the exact growth rates of whole follicles. The number of follicles which began developing during a particular time interval was also determined.

The results show that the number of large follicles fluctuates with the cycle, and that the size of the largest follicles increases during the cycle. Follicles of medium size grow faster at oestrus that at any other time. This is in contrast to the large follicles, in which only minor variations in growth rate were noted. It was moreover shown, that more follicles begin to grow at oestrus than at other periods during the cycle.

It was concluded, that the reduction in the number of small follicles with age is mainly due to follicle development rather than to the degeneration of small follicles.

The time required for the full development of an ovarian follicle is 19 days.
THE IMMUNOREACTIVE GROWTH HORMONE IN SERUM FROM PATIENTS WITH VARIOUS TYPES OF DIABETES MELLITUS
Authors: Yde Hans
Published: December 2008

Employing a chromatographic method the immuno-reactive serum growth hormone was determined in 102 diabetics and 45 controls. The diabetic group consisted of 40 juvenile diabetics and 62 newly diagnosed untreated maturity-onset diabetics. 12 of the juvenile diabetics were newly diagnosed and untreated, while the remaining 28 were long-term diabetics. 33 of the maturity-onset diabetics were non-obese while 29 were obese. All the persons were investigated while fasting in the resting state before getting out of bed. All the groups of diabetics presented an elevated mean fasting serum growth hormone of the same order of magnitude. When the total group of 102 diabetics was analysed against the controls, and also when the 62 maturity-onset diabetics were analysed separately, a statistically significant elevation in the mean fasting serum growth hormone was obtained. This was not the case when the group of 40 juvenile diabetics were analysed separately.

In 10 maturity-onset diabetics the serum growth hormone response to oral glucose was found to be normal as compared to 13 controls.
THE GROWTH HORMONE DEPENDENT INCORPORATION OF SULPHATE INTO THE COSTAL CARTILAGE OF OBESE-HYPERGLYCAEMIC MICE OF DIFFERENT AGES
Authors: Herbai Georg , Westman Sighild , Hellerström Claes
Published: December 2008

The in vivo incorporation of sulphate into costal cartilage was measured in both lean and obese-hyperglycaemic mice of different ages. In 2–10 months old obese mice the sulphate incorporation was found to be markedly increased as compared with lean controls. After a peak value at the age of 4–5 months there was a gradual fall in the sulphation activity. In the lean litter mates a decrease in the sulphation activity was already observed after the first month of life. These findings are considered against the background of the metabolic changes characteristic of the syndrome and the current concepts of the actions of insulin and growth hormone. A possible role of growth hormone in the aetiology of the obese-hyperglycaemic syndrome is discussed.
PITUITARY-ADRENAL FUNCTION IN OLD AGE EVALUATED BY THE INTRAVENOUS METYRAPONE TEST
Authors: Jensen H. Kaalund , Blichert-Toft M.
Published: December 2008

Attempts were made to evaluate indirectly the ability of the pituitary gland to produce ACTH, in relation to increasing age, using the metyrapone test. Twelve aged subjects, average age 77 years, and 11 young control subjects were investigated. The effects of intravenous infusions of 5 g of metyrapone were examined. Plasma cortisol and plasma compound S were checked over a period from 8 a. m. to 8 p. m. Statistical analysis of the results revealed no significant difference between the reactions in the aged and the young. Side effects are discussed.
SUSTAINED RELEASE HORMONAL PREPARATIONS
Authors: Kincl Fred A. , Angee I. , Chang C. C. , Rudel Harry W.
Published: December 2008

Determination of radioactivity in urine, faeces and various organs in rats was used to monitor the absorption of labelled 6-methyl-17α-acetoxy-4,6-pregnadiene-3,20-dione from polydimethylsiloxane implants or after oral administration. Given orally, peak plasma levels were obtained 4 h after administration. It took about 4 days to reach steady plasma levels when PDS implants were used. For a hypothetical biologically effective dose, megestrol acetate plasma levels were about 15 times higher than when an implant was used. Increased plasma levels seen after oral administration were reflected in increased uptake by various tissues. Compared to levels seen in animals having a PDS implant the increase was 40 times higher in liver, 60 times in kidneys, 8 times in adrenals, 6 times in testes and 12 times higher in the brain.
EFFECTS OF TESTOSTERONE AND NANDROLONE AND SOME OF THEIR ESTERS ON THE PSEUDOCHOLINESTERASE ACTIVITY IN THE LIVER AND SERUM AND ON THE SEMINAL VESICLE AND LEVATOR ANI MUSCLE OF THE RAT
Authors: Leeuwin R. S. , Groenewoud E. Th.
Published: December 2008

Testosterone (T), testosterone-propionate (TP), testosterone-phenyl-propionate (TPP), nandrolone (N) (19-nor-testosterone) and nandrolone-phenyl-propionate (NPP) were compared for their effects on the pseudocholinesterase activities in the liver and serum of castrated male rats. In addition changes in the weight of the seminal vesicle and the levator ani muscle were studied. After daily administration of 1 mg of the hormones for ten days, T and TPP showed a more marked depression of the pseudocholinesterase activity and seminal vesicle than the corresponding nor-derivatives. TP and TPP have approximately similar effects, exceeding those of T. On the levator ani N and NPP were more effective than T and TPP. At identical total doses, administration of all hormones with intervals of more than one day, produced less depression of the pseudocholinesterase activity and less seminal vesicle growth than daily administration. The effects on the levator ani were less influenced by varying intervals. At an interval of four days TPP still had a potent effect on the enzyme activity and the seminal vesicle, whereas T was almost without effect. Prolonged administration showed that the effects on the enzyme activity and the seminal vesicle of N and NPP could not reach the maximum effects of T and TPP respectively.
COMPARISON BETWEEN ANTIBODIES TO BOVINE AND HUMAN THYROTROPHIN (TSH) FOR RADIOIMMUNOASSAY IN PLASMA: CROSS REACTION STUDIES WITH CLINICAL RESULTS
Authors: Lemarchand-Béraud Th.
Published: December 2008

The use of bovine and human TSH antisera for the measurement of human plasma TSH by radioimmunoassay has been investigated. The cross reaction between BTSH antiserum and plasma or pituitary HTSH as well as the species specificity of HTSH antiserum has been previously established.

The effects of EDTA, of incubation time, of antiserum and precipitation serum dilutions on the formation of the hormone-antiserum complex were examined in both assays as well as the possible immunological reactivity of BTSH and HTSH antisera with ACTH, HGH, FSH, LH, HCG and HCS.

It was observed that EDTA had no effect on the bovine TSH assay but allowed a faster binding of HTSH - HTSH antiserum, resulting in a short incubation period (2 days). A more diluted precipitating serum than usual was found to increase the precipitation of the antibody complexes in both assays.

No cross-reaction occurred between the BTSH antiserum and human ACTH, HGH, HCS, FSH, LH and HCG. On the contrary, a significant displacement of the HTSH-131I-HTSH antiserum complex was observed with HGH, FSH, LH and HCG (even in low concentrations) but did not occur with ACTH or HCS. When higher levels of these hormones were added, a slightly greater displacement occurred but not in the same proportions.

The values obtained in thyroid diseases by both radioimmunoassays are also reported and compared, but as the reference standards are not the same for both assays, absolute values could not be compared. Nevertheless the variations (increase or decrease) in plasma TSH levels in the different pathological conditions are in good agreement with both assays. Discrepancies were observed only in thyrotoxicosis and in some other cases presenting a slight increase in TSH with the human assay but not with the bovine assay. The bovine assay in the presence of other pituitary hormones has the advantage of exhibiting no cross reactions.
EFFECT OF CORTISONE ON THE GROWTH OF THE VENTRAL PROSTATE, THE DORSOLATERAL PROSTATE, THE COAGULATING GLANDS AND THE SEMINAL VESICLES IN CASTRATED ADRENALECTOMIZED AND CASTRATED NON-ADRENALECTOMIZED RATS
Authors: Tisell Lars-Eric
Published: December 2008

The growth of the ventral and the dorsolateral prostate, the coagulating glands and the seminal vesicles was studied in cortisone-treated and non-treated castrated non-adrenalectomized and castrated adrenalectomized rats. The cortisone was administered in daily doses of 3 mg or 9 mg for a period of 15 days.

Combined castration and adrenalectomy resulted in a greater degree of atrophy of the ventral prostate than castration alone, thus indicating some maintenance effect of the adrenals on the ventral prostate. No differences in the other accessory reproductive organs were demonstrated when comparing non-treated castrated non-adrenalectomized with castrated adrenalectomized rats.

Both doses of cortisone stimulated the growth of the dorsolateral prostate, the coagulating glands and the seminal vesicles, but the larger dose resulted in a greater degree of stimulation. Only the larger dose of cortisone gave histological changes in the ventral prostate indicative of a slight stimulating effect. Catabolic or anti-anabolic effects of cortisone as registered by a decrease in body weight and weight of the levator ani muscle did not inhibit the growth stimulating effect of cortisone on the accessory reproductive organs.

Cortisone stimulated the growth of both the epithelium and the smooth muscle tissue of the glands. The effect on the different accessory reproductive organs after cortisone administration was contrary to previous studies, which demonstrated the stimulating effects of androgens in the rat, in that the ventral prostate was relatively unstimulated.

Possible mechanisms for the stimulation of the growth of the accessory reproductive organs are discussed in the light of our present knowledge of cortisone metabolism and of the secretion in the cortisone-treated rats of hormones which have been found to modify the growth of the accessory reproductive organs.
REGENERATION OF HYPOTHALAMIC NERVE FIBRES AFTER HYPOPHYSECTOMY IN THE GOAT
Authors: Daniel Peter M. , Prichard Marjorie M. L.
Published: December 2008

In goats kept for several months after hypophysectomy it was found that the nerve fibres of the hypothalamo-neurohypophysial tract had regenerated. A posterior lobe-like organ had formed in the neural tissue of the median eminence just proximal to the site where the nerve tract had been severed when the pituitary gland was removed. This new, small, ectopic infundibular process was not only well innervated but also highly vascularised and it contained large amounts of neurosecretory material. Some of the regenerating nerve fibres had grown out from the nerve tract into pars tuberalis and the meninges; many of these nerve fibres carried neurosecretory material. In one goat, not hypophysectomized but with a traumatic lesion of the nerve tract in the pituitary stalk, regenerating nerve fibres had also grown down across the scar of the lesion to reinnervate the degenerate distal part of the nerve tract.

Within the hypothalamus the loss of nerve cells was consistently greater in the supraoptic than in the paraventricular nuclei.
EXCRETION PATTERNS OF 17-KETOSTEROIDS AND 17-HYDROXYCORTICOSTEROIDS IN SURGICAL STRESS
Authors: Tanaka H. , Manabe H. , Koshiyama K. , Hamanaka Y. , Matsumoto K. , Uozumi T.
Published: December 2008

Quantitative determinations of urinary 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids (17-OHCS) were made in 17 males and 8 females before and for 7 days following moderate to major surgery.

The operation caused a marked rise in the excretion of total 17-OHCS. On the other hand, a significant decrease in the excretion of the total 17-KS was found following surgery. The postoperative decrease resulted from a significant decrease in the excretion of C19O2- 17-KS, since the urinary C19O3-17-KS remained almost unchanged following the operation. The postoperative decrease was shown to be of a higher degree in males since the decrease in the excretion of aetiocholanolone and androsterone was more marked in males than in females. Contrary to this, the excretion of both C19O3-17-KS and C19O2-17-KS increased following ACTH injection. From the result, it seems justifiable to assume that the secretion of androgen from the testes may decrease rapidly following operation. It was also demonstrated that the ratio of aetiocholanolone to androsterone increased postoperatively as did the ratio of THF to alloTHF. Furthermore, the ratios of THE to THF and E to F were found to be significantly decreased following surgery.
PLASMA TESTOSTERONE LEVELS FOLLOWING SURGICAL STRESS IN MALE PATIENTS
Authors: Matsumoto K. , Takeyasu K. , Mizutani S. , Hamanaka Y. , Uozumi T.
Published: December 2008

Plasma testosterone levels were determined by the competitive protein binding method of Mayes & Nugent (1968) with slight modifications, in 20 male patients in whom moderate or major surgery had been performed. Preoperative (control) and postoperative blood samples were obtained at 8 a. m. except for immediate postoperative samples. There was a significant decrease in the plasma levels of testosterone immediately and 2 days after moderate and major surgery. The level of testosterone returned toward the control level on the sixth postoperative day after moderate surgery, while after major surgery, the decreased plasma testosterone was maintained for at least 6 days. It is suggested that testicular secretion of testosterone seems to decrease during the postoperative period.
STEROIDS IN NEWBORNS AND INFANTS
Authors: Gustafsson J.-Å. , Shackleton C. H. L. , Sjövall J.
Published: December 2008

The major 3β-hydroxy-Δ5 steroids in the monosulphate and disulphate fractions of faeces from infants 2 weeks to 6 months of age have been assayed by gas chromatography-mass spectrometry. The steroid concentration was highest in a pool of faeces collected from infants 6 to 8 weeks of age, viz: 3β,16α-dihydroxy-5-androsten-17-one, 300 μg/100 g; 3β,16β-dihydroxy-5-androsten-17-one, 360 μg/100 g; 5-androstene-3β,16α,17β-triol, 570 μg/100 g; 3β-hydroxy-5-pregnen-20-one, 810 μg/100 g; 3β-hydroxy-5,16-pregnadien-20-one, 240 μg/100 g; 3β,16α-dihydroxy-5-pregnen-20-one, 1670 μg/100 g; 5-pregnene-3β,20α-diol, 700 μg/100 g and 5-pregnene-3β,16α,20α-triol, 220 μg/100 g. The quantitative relationships between the steroids changed with increasing age of the infants. In the samples collected from infants older than three months of age, 5-pregnene-3β,20α-diol replaced 3β,16α-dihydroxy-5-pregnen-20-one as the principal steroid metabolically related to 3β-hydroxy-5-pregnen-20-one. A comparison between the daily excretion of 3β,16α-dihydroxy-5-pregnen-20-one in the faeces and the published values for the urinary excretion of this steroid, suggests that during early infancy as much steroid is excreted in the faeces as in the urine.
ACTION D'UNE SUBSTANCE PROGESTATIVE SYNTHETIQUE 17α-ALLYL-4-OESTRENE-17β-OL SUR LA DIFFERENCIATION SEXUELLE DES FOETUS DE RAT
Authors: Jost Alfred , Moreau-Stinnakre Marie-Georges
Published: December 2008

Allylestrenol was given to pregnant rats from day 13 to day 20 or 21 of pregnancy. Four different treatments were used: 1) drug given subcutaneously to castrated mother animals 2) drug given subcutaneously to non castrated mothers; 3) drug given by mouth to castrated mothers; and 4) drug given by mouth to non castrated mothers. At term anomalies of the genital tract of the female foetuses were observed in groups 2, 3 and 4; the highest frequency and severity was observed in group 4, and the lowest in group 2. The trans-intestinal route and the presence of the maternal ovaries favour the occurrence of anomalies (by metabolic conversion of the drug?). The males were normal.

In the female foetuses the main anomalies were: complete or partial persistence of the Wolffian ducts in many foetuses; inhibition of the separation of the posterior vaginal cord from the urethra; slight anterior flexure of the uro-genital sinus and some increase in the length of the ano-genital distance; slight anomalies of the genital tubercle.

In females from group 4, reared postnatally until adult, the Wolffian ducts retrogress and there is late development of the vaginal cord (and duct); but the posterior vagina and the clitoris remain abnormal.

The anomalies produced by allylestrenol in females are more similar to those produced by oestrogens than to those produced by androgens (the latter are permanent and include masculinization of the uro-genital sinus). But in pregnant rats given oestrogens the male foetuses are abnormal.

It is not justifiable to interpret the persistence of Wolffian ducts or vaginal inhibition at birth as signs of masculinization when they are not permanent, since similar transient anomalies can be produced by oestrogens.

For these reasons, and also for testing the reproductive capacities of animals treated pre-natally with steroids, the evaluation of the effect of a new compound on the young should include postnatal rearing and study.
NEUTRAL STEROIDS IN URINE DURING PREGNANCY
Authors: Jänne O. , Vihko R.
Published: December 2008

A disulphate fraction of the steroids in the urine of pregnant females was separated by chromatography on Sephadex LH-20. The steroids in this fraction showed the mobility of steroid disulphates on thin-layer chromatography, paper chromatography and high-voltage paper electrophoresis. After solvolysis, the free steroids were fractionated on silicic acid and by thin-layer chromatography. Fractions containing dihydroxylated C19 and C21 steroids were obtained. Using gas-liquid chromatography and gas chromatography-mass spectrometry, the following 18 steroids were identified in the disulphate fraction of neutral steroids in late-pregnancy urine: 5α-androstane-3α,17α-diol, androst-5-ene-3β,17α-diol, androst-5-ene-3β,17β-diol, 18-hydroxyandrosterone, 17α-hydroxydehydroepiandrosterone, 16β - hydroxydehydroepiandrosterone, 3β,17β-dihydroxyandrost-5-en-16-one, 5α-pregnane-3α,20α-diol, 5α-pregnane-3β,20α-diol, 5β-pregnane-3α,20α-diol, 5β-pregnane-3β,20α-diol, pregn-5-ene-3β,20α-diol, 3β,16α-dihydroxy-5α-pregnan-20-one, 16α-hydroxypregnenolone, 3α,21-dihydroxy-5α-pregnan-20-one, 3β,21-dihydroxy-5α-pregnan-20-one, 3α,21-dihydroxy-5β-pregnan-20-one and 21-hydroxypregnenolone. 5α-Pregnane-3β,20α-diol was the most abundant steroid in the fraction analysed, and preliminary quantitative data suggest that sulphate-conjugated pregnanediols and 21-hydroxypregnanolones are excreted mainly as disulphates in late pregnancy urine. The origin of these maternal urinary steroids is discussed.
STUDIES ON THE METABOLISM OF C19 STEROIDS IN RAT LIVER. 6. HYDROXYLATION OF 4-ANDROSTENE-3,17-DIONE IN RAT LIVER MICROSOMES
Authors: Gustafsson Jan-Åke , Lisboa Belisário P.
Published: December 2008

Following incubations of androstenedione with 105 000 × g microsomes of adult male rat liver, 6β-, 6α-, 7α-, 16α-, and 18-hydroxyandrostenedione were isolated by thin-layer chromatography and identified by gas chromatography-mass spectrometry. After incubations with testosterone the only 3,17-dioxo-Δ4-steroids formed were 6β- and 7α-hydroxyandrostenedione. 6β- and 18-Hydroxyandrostenedione were isolated after incubations with 6β- and 18-hydroxytestosterone, respectively. The relative importance of the 17-oxo- and the 17β-hydroxy-pathways in the formation of 3,17-dioxo-Δ4-C19O3 steroids is discussed.
ASSOCIATION OF JUVENILE DIABETES MELLITUS, PRIMARY OPTIC ATROPHY AND PERCEPTIVE HEARING LOSS IN THREE SIBS, WITH ADDITIONAL IDIOPATHIC DIABETES MELLITUS INSIPIDUS IN ONE CASE
Authors: Ikkos D. G. , Fraser G. R. , Matsouki-Gavra E. , Petrochilos M.
Published: December 2008

A family is described showing the association of juvenile diabetes mellitus, optic atrophy, and mild perceptive deafness inherited in an autosomal recessive manner. It is pointed out that concomitant diabetes insipidus has predominantly involved females suffering from this association.
DISTRIBUTION OF MALE AND FEMALE STEROID SEX HORMONES IN SOME ORGANS OF THE MALE RAT
Authors: Tveter Kjell J.
Published: December 2008

[6,7-3H] 17β-Oestradiol with a specific activity of 42.4 Ci/mmole was injected intramuscularly into three to four month old male rats, castrated three days previously. The radioactivity in liver, skeletal muscle, blood, the anterior pituitary gland, the seminal vesicles and in the different prostatic lobes was measured by liquid scintillation counting at different intervals after the administration. A high and prolonged uptake of radioactivity was found in the anterior pituitary gland. The uptake by the accessory sex organs was much lower, but significantly higher than that by skeletal muscle. The uptake by the prostate and the seminal vesicles in castrated animals was similar to that in non-castrated animals.

The pattern of radioactivity uptake in the anterior pituitary gland of castrated male rats given [3H] testosterone was distinctly different from that after administration of [3H] 17β-oestradiol. There was a rapid elimination of radioactivity from the adenohypophysis after the administration of [3H] testosterone.
COAGULATION AND FIBRINOLYTIC STUDIES DURING CONTINUOUS USE OF LOW DOSE GESTAGEN
Authors: Nilsson Inga Marie , Kullander Stig , Åstedt Birger
Published: December 2008

Coagulation factors and the fibrinolytic system were studied in 28 apparently healthy women using low dose gestagen continuously as a contraceptive (0.5 mg chlormadinone acetate daily). The fibrinolytic activity in the blood was also assessed after venous stasis. In 10 of the women determinations were also made of the content of activators of fibrinolysis in the walls of the veins by means of Todd's histochemical method. In contrast to what is seen after the use of contraceptive preparations of combined or sequential type, no changes were found in the factors studied. The increase in the fibrinolytic activity normally produced by venous stasis was not inhibited. The content of activators of fibrinolysis in the walls of the veins was unchanged.
BLOCKADE OF OVULATION IN THE RAT BY ETHANOL
Authors: Kieffer J. David , Ketchel Melvin M.
Published: December 2008

At 1 p. m. on the day of prooestrus (day 0), ethanol (7.9 g/kg, sc), pentobarbital (40.50 mg/kg, ip), or 0.01 n HCl (20 ml/kg, sc) was administered to rats which had previously displayed regular oestrous cycles. Counting of tubal ova at autopsy on the morning of day 1 revealed that ovulation was significantly inhibited by each of these substances. Results from an ethanol-treated group autopsied on the morning of day 2 suggest that the ethanol blockade lasted for at least 2 nights. When administration of ethanol was delayed until 6 p. m. on day 0, ovulation was not inhibited.

Administration, at 2:30 p.m. on day 0, of HCG (100 IU/rat, sc) or LH (93–400 μg/kg, sc) reversed the blockade of ovulation caused by the 3 substances described above.

Despite its conspicuous effects on ovulation, ethanol altered only an insignificant proportion of the vaginal smears taken. Pentobarbital and HCl did not affect the smears of any of the rats tested.

The conclusion was reached that ethanol inhibits ovulation in rats, primarily by blocking the ovulatory surge of LH. This inhibition may account for the previously reported antifertility effect of ethanol in rabbits.
STEROID SYNTHESIS IN A HUMAN VIRILISING ADRENAL CARCINOMA – SOME UNUSUAL FEATURES
Authors: Cameron E. H. D. , Hammerstein J. , Jones D. , Morris S. , Griffiths K.
Published: December 2008

A patient presenting at the Universitäts-Frauenklinik, Berlin with a long history of increasing hirsutism and virilism provided an opportunity to study an unusual form of adrenal hyperfunction. It was found that she behaved abnormally with respect to the dexamethasone suppression test since her highly elevated 17-oxosteroid output further increased by approximately 400% with 8 mg/day dosage. Her basal 17-hydroxycorticosteroid output was elevated but not grossly so, nor did she exhibit the usual signs of Cushing's syndrome of weight increase and florid complexion.

At operation a »tennis ball« size adrenal carcinoma was removed from the left side. Incubation studies were performed on sliced tumour tissue with substrates [1-14C] acetate, [7α-3H] pregnenolone, [4-14C] progesterone and [4-14C] androst-4-ene-3,17-dione. The frozen incubation mixtures were subsequently flown to Cardiff for steroid analysis by reverse radioisotope dilution techniques.

The combined urinary and incubation results suggested that, in vivo, the tumour secreted DHA and not DHA sulphate and that there appeared to be a considerable deficiency of DHA-3β-hydroxysteroid dehydrogenase/Δ5−4-isomerase and of DHA-3β-sulphokinase activities although the steroid-11β-hydroxylase, 17α-hydroxylase and 21-hydroxylase activities seemed unimpaired.
THE ULTRASTRUCTURE OF LIVER CELLS IN WOMEN UNDER STEROID THERAPY
Authors: González-Angulo Amador , Aznar-Ramos Ramón , Márquez-Monter Héctor , Bierzwinsky Guillermo , Martínez-Manautou Jorge
Published: December 2008

An electron microscopic study of liver biopsies of women under steroid therapy was carried out. Liver biopsies taken with a Menghini needle from five healthy young women during their last trimester of pregnancy revealed elongation, gigantism and lamellar osmiophilic matrical inclusions in approximately 10% of the population of mitochondria per cell examined.

Liver biopsies taken from six women with hydatidiform mole and from one women with choriocarcinoma revealed mild focal dilatation and vesiculation of both the rough and smooth endoplasmic reticulum. Mitochondrial modifications were present and included gigantism, pleomorphism and also lamellar osmiophilic inclusions in 10 to 20% of the cases. In one case of hydatidiform mole this change was present in more than 60% of mitochondria examined. The findings are not interpreted as pathological but rather as an exaggeration of a physiological change brought about by an increased metabolic demand during pregnancy or else to a more direct effect of steroid hormones on liver cell organelles.
THE ULTRASTRUCTURE OF LIVER CELLS IN WOMEN UNDER STEROID THERAPY
Authors: Martínez-Manautou Jorge , Aznar-Ramos Ramón , Bautista-O'Farrill Jorge , González-Angulo Amador
Published: December 2008

An electron microscope study was carried out on liver biopsies of fourteen young healthy women under different types of contraceptive therapy. Six women had received an oestrogen-free progestogen (chlormadinone acetate) daily in microdoses for 38 to 44 months. Four were under a combination of oestrogens and progestogens for 63 to 104 months, and four were under sequential therapy, three of these during a six month period and one for a period of 67 months. Liver biopsies were taken from eight women as control material. The changes found in subjects under contraceptive therapy were a moderate dilatation and vesiculation of the rough and smooth surfaced endoplasmic reticulum both in the women treated with microdoses of progestogens, and in those treated with a combination of progestogens and oestrogens. A more marked vesiculation of this organelle was present in those women under sequential medication. Elongation of mitochondria with crystalloid inclusions in their matrices was found in 5 to 10% of the whole population of mitochondria per cell examined in the chlormadinone treated women. The same changes were seen in 20 to 40% in women with combined and sequential therapy. In one case of this last group the mitochondrial modifications were found in more than 60%. Other changes included fatty vacuolation which was more marked when combined and sequential types of treatment were given. Control biopsies were considered as normal. All these changes are regarded as reversible and are thought to represent a response of the liver parenchymal cell to the presence of steroid hormones.
STEROID FORMATION IN PORCINE OVARIAN TISSUE IN VITRO
Authors: Aakvaag Asbjørn
Published: December 2008

The Δ5-3β-hydroxysteroid dehydrogenase activity of a 10 000 × g × 10 min supernatant of porcine ovarian tissue homogenate has been studied using pregnenolone and dehydroepiandrosterone as substrates. The products, progesterone and androstenedione respectively, were isolated by repeated paper and thin layer chromatography in a radiochemically pure form, and the reaction velocities were calculated from the amount of product isolated. The apparent Michaelis-Menten's constants were 2.6 × 10−7 mol/l for pregnenolone and 1.1 × 10−7 mol/l for dehydroepiandrosterone. These low values indicate that the enzyme has very strong affinity for the substrate. This may possibly be the basis for the inability of the porcine ovary to produce androstenedione in vitro via the Δ5-pathway. At a pregnenolone concentration of 4.8 × 10−6 mol/l a significant substrate inhibition was observed, but no such inhibition was seen with dehydroepiandrosterone. A synthetic gestagen, chlormadinone acetate, inhibited 3β-hydroxysteroid dehydrogenase activity. The inhibition was non-competitive with regard to the pregnenolone conversion, and of a more complex type for dehydroepiandrosterone. At equimolar concentrations of substrate and inhibitor, 1.5 × 10−6 mol/, the inhibition was of the order of 80-85%. This inhibition may be quite important in the ovary of the sow because of the inability of this tissue to utilize the Δ5-pathwaw for androstenedione formation.
DISAPPEARANCE RATE OF PROGESTERONE FOLLOWING SIMULTANEOUS REMOVAL OF THE CORPUS LUTEUM AND THE FOETO-PLACENTAL UNIT IN WOMEN
Authors: Fylling Petter
Published: December 2008

Following simultaneous removal of both the corpus luteum and the foetoplacental unit in the first trimester of human pregnancy, the calculated half life (t½) of endogenous progesterone* in peripheral plasma is dependent on the interval between surgery and the intervals between which the samples are taken. During the first 5 to 6 min after uterotomy the disappearance rate is high and the calculated t½ is 6 min. During the following 5 to 6 min a marked inflection of the slope is observed. The calculated t½ from the second part of the curves is 95 min. When tritiated progesterone is given as iv infusion prior to uterotomy, the disappearance curves for labelled and endogenous progesterone parallel each other. However, when labelled progesterone is given as a single iv injection, the second part of the curves is steeper than when iv infusion is given, i. e. t½ is 43 min. The difference might be explained by assuming a two compartment model of distribution and metabolism. In addition, when a single iv injection of tritiated progesterone is given to an intact pregnant woman and a postmenopausal woman, the second part of the curves is fairly similar, the calculated t½ being 45 and 42 min respectively.
THE EFFECT OF DIET AND AGE ON THE RESPONSE TO CALCITONIN IN RATS
Authors: Sørensen O. H. , Hellesen C. , Hindberg Inge
Published: December 2008

The hypocalcaemic effect of calcitonin has been found to be most pronounced in rats younger than approximately 10 weeks.

If the rats are kept on a fixed diet for 24 h before an experiment, a low calcium/high phosphate diet is most suitable. When, however, the diet is maintained for longer periods, the growth rate must be taken into consideration as a high growth rate is essential for an optimal response to calcitonin.

The enhancing effect of an intravenous dose of phosphate on the response to calcitonin has been confirmed.
ROLE OF THE ADRENAL CORTEX IN PERPHENAZINE-INDUCED LACTATION
Authors: Ben-David M. , Sulman F. G.
Published: December 2008

Mammary growth and secretion were induced in adult virgin female rats by daily injections for 5 days of 5 mg/kg perphenazine, a prolactin releaser. In adrenalectomized or adreno-ovariectomized rats, such treatment given immediately after operation induced considerable mammary growth but in no case was milk secretion established. While treatment with cortisol alone (10 mg/kg) did not produce mammary secretion, its combination with perphenazine (5 mg/kg) resulted in maximal mammary growth and copious milk secretion in intact and adrenalectomized animals as well as in oestradiol-primed ovariectomized or adreno-ovariectomized rats. Cortisol also potentiated the galactopoietic effect of perphenazine in lactating animals.

It is concluded that the adrenal cortex is of lesser importance for the perphenazine-induced first stages of mammary growth (mammogenesis), but that the presence of the adrenal hormones is required both for the initiation of milk secretion (colostrogenesis) and for its maintenance (galactopoiesis).
REGULATION OF THE PRODUCTION OF OESTROGEN PRECURSORS IN THE FOETUS
Authors: Oakey R. E. , Heys R. F.
Published: December 2008

Urinary oestrogen excretion was increased in women pregnant with a normal or hydrocephalic foetus who were given metyrapone, a drug known to stimulate corticotrophin secretion by a mechanism which involves inhibition of cortisol biosynthesis. In contrast, women pregnant with an anencephalic foetus showed no change in oestrogen excretion. Since C19 steroids of adrenal origin are the precursors of these oestrogens, it is concluded that androgen production by the foetal adrenal can be stimulated by ACTH secreted by the foetal pituitary in response to a lowering of the concentration of cortisol in the foetal plasma.

Comparison of 17-oxogenic steroid excretion in women with a normal and an anencephalic foetus suggests that the foetal adrenal may make a contribution to the production of these steroids in normal pregnancy.
FURTHER STUDIES ON A SOLUBLE ANDROGEN-MACROMOLECULAR COMPLEX FROM THE RAT VENTRAL PROSTATE
Authors: Unhjem Olav
Published: December 2008

The ability of various steroids and metabolic inhibitors to influence the binding of androgen to soluble macromolecules in the rat ventral prostate was evaluated in vitro. The results obtained revealed some structural requirements of steroids for binding to the macromolecules. An androstane skeleton with the α-configuration of the hydrogen atom at position 5 seemed to be essential for binding as well as a keto group at position 3. N-ethylmaleimide, Na-iodoacetate and p-hydroxymercuribenzoate inhibited the binding of androgen to macromolecules. The androgen-macromolecular complexes appeared to be rather stable at temperatures below 5°C.
STUDIES ON THE UPTAKE AND BINDING OF 5α-DIHYDROTESTOSTERONE BY RAT VENTRAL PROSTATE CELL NUCLEI IN VITRO
Authors: Unhjem Olav
Published: December 2008

Following incubation of rat ventral prostate homogenates with 1,2-3H]-5α-dihydrotestosterone, the steroid was taken up and bound by the nuclei. Sodium chloride extraction of the nuclei removed macromolecules which might at least be partially responsible for the binding. Purified nuclei which were incubated with the radioactive steroid in either Tris-EDTA buffer or a 105 000 × g supernatant fraction prepared from the organ showed a lower degree of binding. Gel filtration chromatography of sodium chloride extracts from these nuclei disclosed binding of steroids to macromolecules. In all the experiments the steroids bound by nuclei consisted of unchanged 5α-dihydrotestosterone.
TRACE ELEMENTS IN THE HUMAN ENDOMETRIUM
Authors: Hagenfeldt K. , Plantin L.-O. , Diczfalusy E.
Published: December 2008

By means of neutron activation analysis, the concentrations of zinc, copper, manganese, sodium and potassium were studied in endometrial biopsy specimens taken from six apparently healthy, normally menstruating volunteers. Quadruplicate endometrial biopsy specimens were obtained from each of the subjects during four consecutive cycles in the following phases: a) early proliferative (days 6–10), b) late proliferative (days 11–14), c) early secretory (days 15–18) and d) late secretory (days 22–27). An analysis of variance of the data revealed that the human endometrium in the early proliferative phase is characterized by significantly elevated concentrations of manganese (P < 0.001), sodium (P < 0.01) and potassium (P < 0.001). On the other hand, the late secretory endometrium is characterized by a highly significant rise in its zinc concentration (P < 0.001), accompanied by a highly significantly decreased concentration of sodium (P < 0.001) and potassium (P < 0.001). The copper concentration of the secretory endometria was significantly higher than that of the proliferative endometria (P < 0.001). The significance of the findings was the same, whether values were expressed per g protein, or per g wet tissue.

It is suggested that the high concentrations of zinc and copper associated with low levels of manganese, sodium and potassium at the expected time of implantation may be a reflection of changes in endometrial enzyme activities.
USE OF LYSIN-VASOPRESSIN IN THE DIFFERENTIAL DIAGNOSIS OF CUSHING'S SYNDROME
Authors: Croughs R. J. M.
Published: December 2008

The plasma cortisol response following intramuscular administration of synthetic lysin-8-vasopressin was measured in nine patients suffering from various forms of Cushing's syndrome. A significant response was obtained in six patients with pituitary dependent Cushing's syndrome, whereas no response was observed in two patients with Cushing's syndrome due to an adrenal tumour and in one patient with an ectopic ACTH syndrome. The possible technical errors which are inherent to this test are discussed in relation to a few contradicting observations from the literature.

In three patients with pituitary dependent Cushing's syndrome the use of lysin-8-vasopressin and metyrapone is compared in the evaluation of pituitary-adrenal reserve capacity during various stages of treatment by unilateral adrenalectomy and external pituitary irradiation.
IMPAIRMENT OF THE PITUITARY-ADRENAL AXIS FOLLOWING PROLONGED THERAPY WITH CORTICOTROPHIN
Authors: Levell M. J. , Stitch S. R. , Noronha M. J.
Published: December 2008

Pituitary-adrenal function was tested in a group of 33 patients with multiple sclerosis who had been treated with corticotrophin for at least 1 year. Assessment was made by measuring the change in the plasma 11-hydroxycorticosteroid concentration following lysine vasopressin (LVP) administration. Ten patients showed abnormally small increases after LVP. Two of the 5 patients with the smallest increases still showed impairment 8 months later. The patients with no withdrawal symptoms had normal or nearly normal increases following LVP. There was an association between the concentration of 11-hydroxycorticosteroids immediately after withdrawal of ACTH and the subsequent response to LVP.