bluuebunny/crossref_metadata_2025 huggingface dataset:
THE RELATIONSHIP BETWEEN STEROID PRODUCTION FROM ENDOGENOUS PRECURSORS AND FROM ADDED RADIOACTIVE PRECURSORS BY RAT ADRENAL TISSUE IN VITRO. THE EFFECT OF CORTICOTROPHIN
Authors: Vinson G. P. , Whitehouse B. J.
Published: December 2008

A method is described for the simultaneous measurement of mass and isotope content of five corticosteroids elaborated during incubations of rat adrenal tissue with added radioactive precursors. The compounds investigated were deoxycorticosterone, corticosterone, 18-hydroxydeoxycorticosterone, 18-hydroxycorticosterone, and aldosterone.

Striking differences were observed between the incorporation of radioactive precursors and the tissues' endogenous precursors into these products. Steroid production from endogenous precursors and from radioactive precursors both showed wide variation, but there was no correlation between the two parameters. Furthermore, pituitary corticotrophin (ACTH) suppression, by prior in vivo administration of cortisol, specifically depressed the mass of subsequently formed corticosterone, while the incorporation of isotope into all the products was unaffected. Addition of ACTH (Synacthen®, Ciba) to the incubation medium partly restored the control condition. Experiments using adrenal capsule tissue and inner zone tissue alone showed that the production of deoxycorticosterone occurred throughout the cortex.

The findings were interpreted as indicating that in rat adrenal in vitro incubations, exogenous and endogenous precursors by no means form a homogeneous pool. It is possible that conversion of radioactive precursors is governed only by the degree of penetration of the endogenous pool, whereas conversion of endogenous precursors may be affected by changes in hydroxylase activities, including those involved in the biosynthetic pathway after the point of pregnenolone formation.
WATER METABOLISM IN THE HYPOPHYSECTOMIZED BRATTLEBORO (DI) RAT
Authors: Bauman John W. , Van Wegen C. , Weil-Malherbe J.
Published: December 2008

To re-examine the relative roles of the anterior and posterior pituitary hormones in diabetes insipidus, the effects of hypophysectomy and hormone replacement therapy in hereditary diabetes insipidus rats (Brattleboro strain) was compared with effect of similar treatment of rats without diabetes insipidus.

In agreement with experiments on surgically induced diabetes insipidus, hypophysectomy sharply reduced water intake in rats with hereditary diabetes insipidus (DI rats). Water intake remained considerably higher, however, in these rats than in the non-DI rats following hypophysectomy. ADH treatment reduced water intake nearly to levels seen in non-DI rats. In water deprivation studies it was found that urine concentrating ability of the hypophysectomized non-DI rats was almost twice that of the hypophysectomized DI rats.

None of the hormones tested restored water turnover of the hypophysectomized DI rats to that seen in sham operated controls. ACTH and T3 increased water intake, but not to levels seen in DI rats with intact pituitary glands.

These experiments lead us to concur with those who hold that maximal flow in diabetes insipidus requires the participation of the anterior pituitary hormones. In addition these experiments indicate that ADH or ADH like material is physiologically functional in hypophysectomized rats (other than the Brattleboro strain), and that its presence accounts for the absence of diabetes insipidus following pituitary removal.
THE DEVELOPMENT OF THE MOUSE OVARY FROM BIRTH TO MATURITY
Authors: Peters Hannah
Published: December 2008

Changes occur in the infant ovary which develop the structurally simple organ at birth to a highly complex one in the maturing animal. The ovary in the immature mouse is not a dormant organ but one that is characterized by a continuous growth and development and a concurrent continuous degeneration of oocytes and follicles. The stroma cells which are present in the ovary at birth are apparently a pool of cells with multiple potentialities, which contribute to the development of the earliest granulosa and theca cells. The interfollicular stroma of the juvenile ovary, however, originates from collapsing and contracting follicles. The quantitative changes in the oocyte and follicle population during the immature period lead to a marked reduction in the total number of oocytes and a simultaneous numerical increase in follicles at different stages of development. Factors influencing oocyte atresia and follicle development in the immature mouse are discussed.
FOLLICLE GROWTH IN THE IMMATURE MOUSE OVARY
Authors: Pedersen Torben
Published: December 2008

The growth of follicles in the immature mouse ovary was investigated in autoradiographs prepared after pulse-labelling with tritiated thymidine. Three parameters, which determine follicle growth were estimated:

The number of follicles present in the ovary at different ages.

The time it takes follicles to grow from one stage of development to another. This was calculated from the total number of granulosa cells in these stages and from their doubling times. The doubling time of granulosa cells was determined from their labelling index and the duration of their DNA-synthesis phase.

The number of follicles, which start on their development at different ages.

It was found, that the follicle development is not constant in the period from birth to maturity, but varies considerably. More follicles start to grow in the young than in the older immature mouse. Moreover the follicles grow faster early in life than later. The development from a follicle with one layer of granulosa cells to one with several layers and antrum formation takes about 10 days in the first half of the immature period, while it takes about 16 days as the animal approaches maturity. It was furthermore shown, that about 850 follicles start to grow in the immature period.
STERILITY DUE TO RADIOACTIVE PHOSPHORUS IN MICE: A STUDY OF OVARIAN COMPENSATORY HYPERTROPHY
Authors: Holmberg E. A. D. , Pasqualini Christiane Dosne , Rabasa S. L.
Published: December 2008

The administration of 60 μCi of 32P to pregnant BALB mice induced sterility in the offspring due to destruction of the gonads. The testes presented aspermatogenesis, trophic Leydig cells and normal secondary sex characteristics. The ovaries showed re-absorption of the primary and secondary follicles, absence of ovulation and progressive luteinization of the stroma, as well as atrophy of the uterus and dioestrus. Apart from the alteration in the pituitary feedback mechanism as a result of these gonadal lesions, a direct effect of 32P on the hypothalamic-hypophyseal axis was observed. In these animals the uptake of 32P by the hypothalamus was significantly lower than in normal or castrated controls. The compensatory hypertrophy of the ovary, 1 month after hemi-castration was significantly decreased. The intrarenal grafting of a normal ovary in a 32P-treated host led to lower compensatory hypertrophies than in normal hosts, as determined both 1 and 3 months after grafting. These results were obtained in female and male hosts of 1, 3 and 6 months of age, with transplanted ovaries aged 1, 3 and 6 months respectively. In all the groups, ovarian compensatory hypertrophy was higher in the male than in the female hosts, but the differences between 32P treated and normal hosts were more significant in the females. This difference persisted even when castration of the host was carried out 1 month before grafting of the ovary and when 32P was administered 1 day after removal of the gonads, thus eliminating any secondary effect. It can be concluded that the administration of 32P during foetal life, apart from causing lesions in the gonads, has a direct effect on the hypothalamus with subsequent alteration in the output of gonadotrophins.
LONG-ACTING THYROID STIMULATOR (LATS) IN TOXIC NODULAR GOITRE, TOXIC ADENOMA AND GRAVES' DISEASE
Authors: Lamberg B.-A. , Gordin A. , Viherkoski M. , Kvist G.
Published: December 2008

The long-acting thyroid stimulator (LATS) was determined by means of the McKenzie assay in 68 patients with hyperthyroidism. The patients were classified into the following groups:

Group 1. Graves' disease (diffuse goitre with hyperthyroidism with or without exophthalmos). Of the 35 patients tested 25 (71 %) were LATS-positive.

Group 2. Graves' disease with nodular goitre (nodular goitre with hyperthyroidism and with exophthalmos). The present series includes only 4 such patients, although this combination is by no means uncommon in Finland. Two of the patients were LATS-positive. It has been suggested that these patients represent Graves' disease superimposed upon endemic nodular goitre.

Group 3. Toxic nodular goitre. The present series comprises 23 patients with toxic multinodular goitre, of whom 10 (44%) were LATS-positive. In view of the findings on thyroid palpation, on thyroid scintigraphy, the presence or absence of LATS in the blood and some other criteria, these patients can be divided into two categories, (a) one with Graves' disease superimposed upon nodular goitre of endemic origin (see group 2) and (b) the other with classical multinodular goitre. Analysis of the scintigrams showed that in some patients (with either exophthalmos or LATS in the blood and nodular goitre = Graves' disease + nodular goitre) it was not the nodules that were activated but the paranodular tissue, a finding which gave a scintigram typical of patients with classical Graves' disease. In some LATS-positive cases, however, some nodules were also activated to the same extent. The difference between these scintigrams and those typical of classical multinodular goitre is particularly stressed

since in Finland »toxic nodular goitre« is the prevailing type of hyperthyroidism.

Group 4. Single toxic adenoma. Two patients out of 6 were LATS-positive. This is in contrast to the findings of other authors according to which LATS has never been found in patients with toxic adenoma. A hypothesis is put forward that in these patients subclinical Graves' disease (LATS in the blood) coincided with a primarily autonomous, hyperactive but not necessarily toxic single thyroid adenoma, which was more susceptible to the stimulating activity of LATS than the surrounding tissue.
THYROXINE BINDING PROTEINS OF MOUSE SERUM AT PHYSIOLOGICAL pH
Authors: Gordon Amirav , Coutsoftides Theodore
Published: December 2008

The binding properties of mouse serum for L-3'5'3,5 tetraiodothyronine (T4) and L-3'3,5, triiodothyronine (T3) were investigated by agar gel electrophoresis in several buffer systems at pH 7.4 and pH 8.6. Mouse serum binds T4 and T3 in the albumin and the α-globulin regions; these were designated as mouse thyroxine binding albumin (TBA) and mouse thyroxine binding globulin (TBG). The fractional distribution of T4 varied with the buffer, the pH and the molarity of the system. Mouse TBG contained two binders, the first with a binding capacity of 14.0 × 10−7 m and the second with a binding capacity of 54.3 × 10−7 m. The effect of various inhibitors on thyroxine binding by mouse TBG suggests that mouse TBG behaves in some respects like human TBG and in other respects like human thyroxine-binding pre-albumin (TBPA).
THE FREQUENCY OF DIABETES MELLITUS IN PATIENTS WITH TURNER'S SYNDROME AND PURE GONADAL DYSGENESIS
Authors: Nielsen J. , Johansen K. , Yde H.
Published: December 2008

Glucose tolerance, plasma insulin and growth hormone response to a glucose load were studied in 10 patients with Turner's syndrome and 3 patients with pure gonadal dysgenesis. It was found that 60 per cent of the patients with Turner's syndrome had a diabetic GTT. This is a frequency which is significantly higher than expected. None of the patients with pure gonadal dysgenesis had a diabetic GTT.

The diabetes in patients with Turner's syndrome was of a mild type as is most frequently found in maturity-onset diabetes. The insulin response was, however, different from what is usually found in maturity-onset diabetes. The patients with Turner's syndrome showed a brisk rise and prolonged high levels of plasma insulin after glucose ingestion. An early plasma growth hormone peak was found in patients with Turner's syndrome. The significance of this finding for the pathogenesis of mild diabetes in patients with Turner's syndrome is discussed together with other possible aetiologic and pathogenetic factors.
STUDIES ON THE INFLUENCE OF AGE ON OESTROGENS IN POST-MENOPAUSAL WOMEN WITH ATROPHIC ENDOMETRIUM AND NORMAL LIVER FUNCTION
Authors: Procopé B.-J. , Adlercreutz H.
Published: December 2008

A group of 104 post-menopausal women, who were at least 50 years old and with a time lapse of at least 2 years since the last menstruation, were investigated for their urinary oestrogen content. All the women had an atrophic endometrium as judged by histological investigation of a biopsy specimen. In 66 of the subjects the mean value of the karyopyknotic and eosinophilic indices in the vaginal smear was also calculated. The women, whose ages ranged from 50 to 79 years, were divided into 6 age groups. The median values for the excretion of oestrone, oestradiol, oestriol and total oestrogens and the mean karyopyknotic and eosinophilic indices for all age groups were very constant though there was considerable individual variation. It was also shown that the median values for all subjects were practically identical with those of 57 ovariectomized women reported in a previous study. It is concluded that in the majority of post-menopausal women with atrophic endometrium the ovarian contribution to the production of oestrogens is insignificant. It can also be concluded that with increasing age the normal liver does not significantly change the metabolism of oestrogens in post-menopausal women, as judged by the excretion of oestrone, oestradiol and oestriol, and the oestrogenic effect on the vaginal smear.
FURTHER STUDIES ON THE EFFECT OF ORAL CONTRACEPTIVES ON ENDOCRINE FUNCTION WITH SPECIAL REFERENCE TO LUTEINISING HORMONE EXCRETION
Authors: Papanicolaou A. D. , Loraine A. , Jackson Margaret C. N.
Published: December 2008

Serial assays of luteinising hormone (LH) and pregnanediol in urine have been performed in four women during and following long term therapy with oral contraceptives. One subject was treated with a progestogen-oestrogen mixture, another with a progestogen alone and two with a sequential regime. In three subjects there was definite evidence for the resumption of ovulation in the first post-treatment cycle; in the fourth the evidence was less clear cut.

None of the patients showed suppression of urinary LH activity as a result of medication, and in all four the fiducial limits of individual assays in the treatment and post-treatment cycles overlapped to a considerable extent. One woman receiving sequential therapy showed a midcycle LH peak in the post-treatment but not in the treatment cycle. These findings are compatible with the view that long term therapy with oral contraceptives does not produce any deleterious effects on pituitary gonadotrophic function.

In one subject the short term effect of chlormadinone acetate administered continuously in low dosage was investigated. The compound produced little effect on either LH or oestrogen output, but may have inhibited ovulation as judged by urinary pregnanediol assays.
OESTROGEN – ANTI-OESTROGEN INTERACTION: EFFECT OF U11100A, MRL-41 (CLOMIPHENE) AND U11555A ON OESTROGEN INDUCED UTERINE GLYCOGEN AND PROTEIN SYNTHESIS IN THE RAT DURING DELAYED IMPLANTATION
Authors: Mohla Suresh , Prasad M. R. N.
Published: December 2008

A comparative study of three non-steroidal anti-oestrogens (a dihydronaphthalene, UlllOOA; a diphenylindene derivative, U-11555A and MRL-41 (clomiphene) was made in order to study their mode of action and their interaction with oestrogen induced biochemical changes in the uterus.

Pretreatment with UlllOOA, clomiphene or U11555A effectively blocked the oestrogen induced increase in uterine glycogen and protein synthesis. However, all the three compounds tested were found to be uterotrophic; clomiphene also increased uterine glycogen while U11555A showed a transient oestrogenic action in increasing uterine protein. Clomiphene and U11100A have been shown to inhibit the uptake of oestrogen at the receptor sites. Our results may be interpreted as indicating that pretreatment with these compounds (U11100A, clomiphene or U11555A) blocked the uterine receptor sites in such a manner so as to render ineffective the action of oestrogen administered subsequently.
PLASMA THYROTROPHIN LEVELS IN THYROID DISEASE AND EFFECT OF TREATMENT
Authors: Lemarchand-Béraud Th. , Scazziga B. R. , Vannotti A.
Published: December 2008

A radioimmunoassay has been developed and was applied in a first study to the determinations of human plasma TSH in normal subjects. In the present work a systematic study was made of the relation between the pituitary and the thyroid gland in thyroid disease, and on the effect of various forms of treatment in 750 patients. Normal values for adults of both sexes were found to be 0.19 mU/ml, referred to the international bovine TSH standard (USP).

No TSH was found in pituitary hypothyroidism. Elevated levels, up to fifteen times those of normal subjects, were found in myxoedema. The low initial values in all forms of thyrotoxicosis were followed by modifications during treatment depending on the kind of treatment used. Every qualitative or quantitative deficiency of thyroid hormone secretion was accompanied by an elevation of TSH (euthyroid nodular goitre, thyroid carcinoma, subacute thyroiditis and Hashimoto's disease) and treatment with thyroid hormones induced a rapid fall in plasma TSH. The action of lysine vasopressin was also studied.
DETERMINATION OF CORTISOL IN CAPILLARY BLOOD FROM MAN
Authors: Jansen Jens Aas , Schou Jens , Hvidberg Eigill
Published: December 2008

A spectrophotofluorometric micromethod for the determination of cortisol in plasma is shown to give satisfactory results when used on plasma from ear lobe blood as compared with determinations on simultaneously drawn vein puncture blood. 200 μl heparinized plasma is sufficient for a double determination. The method allows frequent multi-analysis of plasma cortisol, only small amounts of blood are drawn and there is little inconvenience for the patient.
IN VITRO STOFFWECHSEL VON [4-14C]-TESTOSTERON IN VESICULARDRÜSEN VON RATTEN
Authors: Henrichs Helmut R. , Dirscherl Wilhelm
Published: December 2008

Experiments to elucidate the in vitro metabolism of [4-14C] -testosterone in seminal vesicles of rats are described. Besides unchanged testosterone, the following metabolites were isolated and identified by their chromatographic behaviour: 3α,17β-dihydroxy-5α-androstan, androst-4-ene-3,17-dione, 17β-hydroxy-5α-androstan-3-one, 3β-hydroxy-5α-androstan-17-one, 5α-androstane-3,17-dione. The first 3 of these compounds were also identified by the inverse isotope dilution technique. The reduction in ring A yields 5α-metabolites only.
THE ESTIMATION OF 3α-HYDROXY-5α-ANDROST-16-ENE AND OTHER C19-Δ16-STEROIDS IN URINE BY GAS-LIQUID CHROMATOGRAPHY
Authors: Brooksbank B. W. L. , Gower D. B.
Published: December 2008

A method is described for the quantitative estimation of C19-Δ16-steroids in human urine. After extraction and preliminary purification by the method of Brooksbank & Haslewood (1961), the steroids were analyzed as chloromethyl dimethylsilyl ethers by gas-liquid chromatography. The specificity, accuracy and precision of the method were found to be satisfactory and comparison with the colorimetric method of Brooksbank & Haslewood (1961) for urinary 3α-hydroxy-5α-androst-16-ene showed a high correlation coefficient, r = 0.97 (P < 0.001). Figures are given for the urinary excretion rate of 3α-hydroxy-5α-androst-16-ene of normal men and women and of some women suffering from hirsutism and from adrenocortical overactivity. The values are given for 3α-hydroxy-5β-androst-16-ene and 3β-hydroxyandrosta-5,16-diene in pools of urine from healthy men and women.
ACETATE AND CHOLESTEROL METABOLISM IN THE HUMAN FOETO-PLACENTAL UNIT AT MIDGESTATION
Authors: Telegdy G. , Weeks J. W. , Wiqvist N. , Diczfalusy E.
Published: December 2008

Two midgestation placentas were perfused with 2.5 mCi of uniformly labelled 14C-sodium acetate plus 2.5 mCi cholesterol-7α-3H. and two complete foeto-placental units were perfused with 5.0 mCi of 14C-labelled sodium acetate plus 5.0 mCi of cholesterol-7α-3H. The perfusions were carried out at 35–36°C for 90 min.

After the perfusion of the isolated placentas, the following 3H-labelled steroids were isolated from the placentas as well as from the perfusates in a radiochemically homogeneous form: pregnenolone (3β-hydroxy-pregn-5-en-20-one), progesterone (pregn-4-ene-3,20-dione), 20α-dihydroprogesterone (20α-hydroxy-pregn-4-en-3-one), 20β-dihydroprogesterone (20β-hydroxy-pregn-4-en-3-one), 17α-hydroxy-pregnenolone (3β,17α-dihydroxy-pregn-5-en-20-one),dehydroepiandrosterone(3β-hydroxy-androst-5-en-17-one) and 17β-oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).

The same compounds were also isolated from the placentas following the perfusion of the complete foeto-placental units.

With the exception of pregnenolone and progesterone, all steroids were isolated in minute quantities.

None of the steroids isolated contained any 14C-label.

It is concluded that the midgestation human placenta is not capable of carrying out any de novo steroid synthesis from acetate and that cholesterol is an obligatory precursor in placental steroidogenesis.
COMPARISON BETWEEN OESTROGENIC AND ANTIFERTILITY ACTION OF BIS(P-ACETOXY PHENYL)CYCLOHEXYLIDENE METHANE (F 6066; SEXOVID®; CYCLOFENIL NFN) IN THE MOUSE
Authors: Carlborg Lars
Published: December 2008

A diphenyl-ethylene derivative (F 6066; Cyclofenil, NFN) previously described as a weak oestrogen was compared with oestradiol benzoate (OE2B) as an abortifacient in pregnant mice. Evaluation of the respective oestrogenic potencies, using the mouse uterine weight test was performed. This test indicated that oestradiol benzoate was about 2000 times more active than F 6066. If the compounds were given daily on days 2–5 of pregnancy the corresponding ratio was 1000, indicating a relatively higher (2 × abortifacient action of F 6066. Day 2 of pregnancy appeared to be the most sensitive for either drug. When given only on this day, however, the ratio abortifacient/oestrogenic potency did not differ from that of OE2B. The small differences recorded may depend on biological variations and differences in duration of action. Compound F 6066 appeared most likely to interfere with pregnancy because of its oestrogenic properties.
MODE OF ACTION OF TESTOSTERONE PROPIONATE ON THE SECRETION AND RELEASE OF LUTEINIZING HORMONE (LH) IN THE CASTRATED RAM
Authors: Pelletier Jean
Published: December 2008

The mode of action of a single injection of testosterone propionate on LH secretion and release has been studied in the castrated ram.

In the first experiment, six castrated rams were injected intramuscularly with 400 mg of testosterone propionate, and the plasma LH levels were assayed by radioimmunoassay: on the first day after treatment, the plasma LH levels decreased significantly (P < 0.001), then remained at a very low level for 5–7 days; initial LH levels were restored by day 9. Testosterone propionate thus blocks the discharge of LH.

A second experiment was then performed. Castrated rams in groups of 3 were killed either without treatment (control group D0), or 2, 7 or 9 days after the injection of testosterone propionate (groups D2, D7 and D9). In addition to the plasma LH, hypophyseal LH and hypothalamus LRF (LH releasing factor) were measured: the LRF activity was assessed by the quantity of LH released in vitro from the hypophysis of castrated rats blocked with testosterone propionate. The LH released into the incubation medium and the hypophyseal LH of the ram were measured by the ovarian ascorbic acid method and by radioimmunology.

The results of the plasma LH assays were comparable to those in the first experiment: plasma LH was significantly decreased in group D2, increased in group D7 and was restored in group D9. Hypophyseal levels, on the other hand, increased in groups D2 and D7, but were comparable to the controls in group D9, indicating that the injection of testosterone propionate had little or no effect on LH secretion.

Finally, the LRF activity was considerably reduced in group D2 (P<0.001) as compared with the controls (D0), but similar to the control values in group D9. Although secretion appeared normal, the decreased plasma LH levels in group D2 indicated that LRF had not been released; consequently the decrease in LRF observed can be interpreted as being due to an inhibition of its synthesis under the influence of testosterone propionate.
STEROID FORMATION IN PORCINE OVARIAN TISSUE IN VITRO
Authors: Aakvaag Asbjørn
Published: December 2008

Slices of non-luteinized porcine ovaries have been incubated in the presence or absence of human chorionic gonadotrophin (HCG) and exogenous radioactive substrates. Progesterone, 17α-hydroxyprogesterone and androstenedione were isolated in a radiochemically pure form. The chemical mass and the specific activity were determined by gas liquid chromatography and liquid scintillation spectrometry.

HCG stimulated the rate of formation of androstenedione in the absence of exogenous substrates with a factor of 4–8. In the presence of pregnenolone or progesterone at a concentration of about 2 × 10−6 mol/l the stimulatory effect of HCG was either abolished or markedly reduced. The conversion of exogenous progesterone to androstenedione was reduced in response to HCG indicating that the capacity of the tissue to convert progesterone to androstenedione was limited, and that the limit was reached at this rather low substrate concentration. These findings furthermore suggest that the endogenous rather than the exogenous radioactive substrate will be »preferred« by the tissue. The observations demonstrate the necessity of measuring both the radioactivity and the chemical mass of the products in investigations of this type using radioactive substrates.

The formation of progesterone from endogenous substrates was also stimulated by HCG. [1-14C] acetate and [7α-3H]cholesterol were not utilized by the tissue for steroid formation. Exogenous [4-14C] pregnenolone and [7α-3H] progesterone in similar concentration were both utilized for production of 17α-hydroxyprogesterone and androstenedione. HCG had no effect on the relative utilization of the radioactive substrates.
BIOLOGICAL EFFECTS OF HUMAN URINARY FOLLICLE STIMULATING HORMONE
Authors: Petrusz P. , Robyn C. , Diczfalusy E.
Published: December 2008

The biological effects of human follicle stimulating hormone (FSH) preparations were studied in intact immature female mice and in hypophysectomized immature female and male rats, following the complete neutralization of the luteinizing hormone (LH) content of human urinary menopausal gonadotrophin (HMG) preparations having – prior to neutralization – FSH:LH ratios ranging between 1.0 and 500.0. Neutralization of LH was achieved by the addition of rabbit anti-human chorionic gonadotrophin (HCG) sera of known anti-LH potency. The amount of anti-LH employed was 1.5 to 730 times more than that required for 100% neutralization.

In intact immature female mice, such »LH-free« FSH preparations induced an increased ovarian weight, follicle stimulation, as well as a uterine weight increase.

In immature hypophysectomized female rats, »LH-free« FSH preparations induced ovarian weight increase, growth and maturation of the Graafian follicles without repair of the deficient interstitial cells and without any signs of luteinization. These ovarian changes were associated with an increase in uterine weight and with vaginal cornification. In view of these data, it is concluded that human urinary FSH per se is capable of inducing oestrogen synthesis in hypophysectomized female rats.

In immature hypophysectomized male rats, »LH-free« FSH preparations induced testicular enlargement without any stimulation of the testicular interstitial cells and without any growth of the ventral prostate and seminal vesicles. The same effects were obtained following a prolonged administration (3 weeks); spermiogenesis was stimulated, but no mature spermatozoa were found.
ENDOCRINE PROFILE OF A NEW PROGESTATIONAL STEROID
Authors: Boris Alfred , De Martino Louis , Trmal Thelma
Published: December 2008

In the Clauberg-McPhail assay Ro 7-2133 (4,6-Dichloro-17α-hydroxy-pregna-4,6-diene-3,20-dione,acetate) was found to be at least fifty times more potent than progesterone. Ro 7-2133 did not manifest antigonadotrophic, androgenic, anabolic, uterotrophic, thymolytic, or anti-inflammatory activities in rats at dosages which were substantially above the progestational dose in rabbits. The compound did not cause adrenal atrophy in rats after ten days of treatment and did not interfere with fertility or fecundity in mice. Ro 7-2133 was weakly anti-androgenic in castrated rats and intact chicks and showed weak antagonism toward the uterotrophic activity of oestradiol in immature rats.
STUDIES ON THE INACTIVATION OF PANCREOZYMIN CONCENTRATES
Authors: Hartiala Kaarlo , Gershbein Leon L.
Published: December 2008

The loss in hormonal activity resulting on incubation of pancreozymin concentrates with canine blood serum at 37°C has been investigated. The test extracts comprised (SI), a solid obtained from treatment of a salted acid extract of the upper intestinal mucosa with trichloroacetic acid and the amine precipitate, (AP), derived from SI. The decrease in activity was determined in relation to an incubated concentrate-saline solution in dogs with the main pancreatic duct cannulated. Fluid secretion was promoted by potent secretin preparations in saline administered by single injection or by continuous infusion. As based on the total amylase content of the pancreatic juice samples, the hormonal concentrates underwent rather small losses in activity, the AP requiring higher dilutions with serum for an effect as compared to SI. Canine liver extract and a hog kidney diamine oxidase concentrate caused inactivation of pancreozymin products but bovine and canine plasma protein fractions, heavy metal salt and thiol solutions and possibly, human urine, were without action.
CHANGES IN THYROXINE-BINDING GLOBULIN LEVELS IN THYROTOXICOSIS AND IN HEALTHY SUBJECTS AFTER TRIIODOTHYRONINE ADMINISTRATION
Authors: Harvey R. F. , Williams E. S. , Ellis S. , Ekins R. P.
Published: December 2008

Thyroxine-binding globulin (TBG) levels were found to be significantly lower in 40 thyrotoxic patients than in 70 healthy subjects. A similar mean fall in TBG of 18% was produced by administration of 'physiological' doses of triiodothyronine to healthy volunteers. However, intramuscular injection of thyroid-stimulating hormone (TSH) had no consistent effect on the level of TBG as measured up to 4 days after injection. These findings are believed to explain the anomalous results described by earlier workers. It is suggested that TBG concentration is regulated by unknown mechanisms subject to the influence of many hormones, including triiodothyronine.
STEROID EXCRETION AND BIOSYNTHESIS WITH SPECIAL REFERENCE TO C19-Δ16-STEROIDS IN AN INFANT WITH A VIRILIZING ADRENOCORTICAL CARCINOMA
Authors: Gower D. B. , Daly J. R. , Snodgrass G. J. A. I. , Stern Margaret I.
Published: December 2008

A case of a 15-month old girl with a virilizing adrenocortical carcinoma is described. Three C19-Δ16-steroids, 3α-hydroxy-5α-androst-16-diene, 3α-hydroxy-5β-androst-16-ene and 3β-hydroxy-androsta-5,16-diene, have been obtained from the glucuronide fraction of the urine and identified by column and gas-liquid chromatographic techniques. Estimation of these compounds, not normally present in infants' urine, showed that adult female amounts were being excreted, although post-operatively very little was detected. Androsterone, aetiocholanolone and especially dehydroepiandrosterone were present in excessive amounts preoperatively; approximately one-third of the dehydroepiandrosterone was excreted as glucuronide, the rest as sulphate. The adrenal tumour metabolized [4-14C] pregnenolone and [4-14C] progesterone to 4.7% and 0.15% respectively of 3β=hydroxy-androsta-5.16-diene. The evidence for biosynthesis of this compound from progesterone supports that obtained by other workers for the production of Δ5- from Δ4-steroids. Labelled androstenedione was also obtained from both substrates and 1 1β-hydroxyandrostenedione from progesterone. Only small quantities of radioactivity were recovered in the glucuronide and sulphate fractions from the tissue incubations.
INFLUENCE OF AN ANTIANDROGEN (CYPROTERONE) ON THE GONADOTROPHIC FUNCTION OF THE PITUITARY GLAND, ON THE GONADS AND ON METABOLISM IN NORMAL MEN
Authors: Rausch-Stroomann J.-G. , Petry R. , Hocevar V. , Mauss J. , Senge Th.
Published: December 2008

Treatment with Cyproterone 200 mg/d induced no increase of total gonadotrophins in normal subjects. Plasma testosterone was elevated during the period of treatment. An alteration in the ratio LH/FSH has been suggested.

Urinary 17-KS showed no uniform pattern, but 17-KGS were always significantly elevated during Cyproterone treatment. Seminal fluid examinations showed no effect of Cyproterone (100 and 200 mg/d, total dose 4.2–38.6 g within 9 months) on spermatogenesis in 6 adults with normal gonadal function. No increase of spermatogenesis has been observed under treatment with Cyproterone (100 mg and 200 mg/d, total dose 3.5–35.4 g within 8 months) in 7 patients with oligospermia. Over a period of 21 days no influence of Cyproterone (200 mg/d) has been observed on the function of adrenal cortex, concerning cortisol- and aldosterone production, on the carbohydrate and lipid metabolism and on liver function in 5 subjects.
A RADIOIMMUNOASSAY FOR PARATHYROID HORMONE IN MAN
Authors: Schopman W. , Hackeng W. H. L. , Lequin R. M.
Published: December 2008

Bovine parathyroid hormone (PTH) was purified up to the Sephadex-stage. The biological activity of the preparations was about 2000 U/mg solid material. Rabbits and guinea-pigs were immunized with crude and Sephadex-purified material. Antisera elicited in two guinea-pigs proved to be useful for further studies. Purification of 125I-labelled bovine PTH was carried out by adsorption to and desorption from antibodies or by means of microfine silicate. The purified labelled hormone showed excellent binding to the antibodies. Maximum sensitivity of the assay system of 10 pg per incubation medium could be achieved by a pre-incubation method. The selectivity of the system was studied.
HORMONAL STEROIDS IN THE ARMADILLO, DASYPUS NOVEMCINTUS
Authors: Brinck-Johnsen Truls
Published: December 2008

[4-14C]Testosterone, [4-14C]androst-4-ene-3,17-dione and [1,2-3H]androst-4-ene-3,17-dione were aromatized by armadillo placental preparations in vitro to form oestrone and 17β-oestradiol. The armadillo placenta possessed this steroid aromatizing enzyme system both early and late during pregnancy.

Conclusive evidence for the biosynthesis of oestrone and 17β-oestradiol was established by obtaining constant tritium/carbon-14 ratios during several thin layer chromatographic steps in conjunction with derivative formation, after first adding authentic oestrogen with isotope label different from that of the labelled precursor. In spite of the placental capacity for oestrogen biosynthesis, extraction of plasma, urine and placental tissue revealed only very small, although analytically significant amounts of oestrone, 17β-oestradiol and oestriol, assayed by highly sensitive spectrofluorometric techniques.
EFFECTS OF COMBINED AND LOW-DOSE GESTAGEN ORAL CONTRACEPTIVES ON PLASMA LIPIDS; INCLUDING INDIVIDUAL PHOSPHOLIPIDS
Authors: Larsson-Cohn U. , Berlin R. , Vikrot O.
Published: December 2008

Free fatty acids (FFA), triglycerides (TG), total and free cholesterol, total phospholipids and the individual phospholipids lysolecithin, sphingomyelin, lecithin and cephalin were determined in four groups of women, each consisting of nine or ten subjects. The determinations were performed before treatment and about every third month during one year of medication. Two combined drugs, Anconcene® (Chlormadinone acetate = CMA, 3 mg + mestranol 0.1 mg) and Conluten® (Norethindrone = NET, 2 mg + mestranol 0.1 mg) and two low-dose gestagen drugs, CMA 0.5 mg and NET 0.4 mg were used.

FFA decreased in the Anconcene group. TG increased among those taking Anconcene, Conluten and NET. Slight increases of cholesterol were noted in the two groups taking combined drugs. Total phospholipids were increased in the Anconcene group and the Conluten group. Among the individual phospholipids, changes appeared similar to those found during pregnancy. They were most pronounced in the Anconcene group.

It seems that it is the oestrogenic component of the combined drugs that is responsible for many of the alterations. It is suggested that the testosterone derivative NET but not the progesterone derivative CMA may have anti-oestrogenic effect in this connection.
CONVERSION OF ANDROGENS INTO OESTROGENS BY HYDATIDIFORM MOLES IN VITRO
Authors: Houtzager Hans L. , van Leusden Hubertus A. , Siemerink Maria
Published: December 2008

[1,2-3H] and [7α-3H] testosterone* and [4-14C] androstenedione incubated with hydatidiform mole tissue are converted into oestrone and oestradiol. No conversion into oestriol was observed. The radiometabolites were purified using TLC in different systems and crystallization to a constant specific activity and/or 14C/3H ratio.

Appropriate corrections were made for endogenous production of steroids during the incubation.

From time-experiments with [4-14C] androstenedione and [7α-3H] or [1,2-3H] testosterone it appears, that androstenedione is a more effective precursor than testosterone for oestrone and oestradiol.

Equilibrium oestrone ⇋ oestradiol is established more rapidly than androstenedione ⇋ testosterone. Conversion of androstenedione into oestrone is more effective than conversion of testosterone into androstenedione. Data are reported in agreement with the hypothesis of a direct pathway from testosterone to oestradiol in the shorter periods of incubation.

Determination of the endogenous pools of oestrone, oestradiol, testosterone and androstenedione synthesized during the incubations indicates that oestrone is the most important steroid produced in vitro.
THE EFFECT OF ALTERATIONS IN ADRENOCORTICAL FUNCTION ON THE MOUSE UTERINE WEIGHT RESPONSE TO HUMAN CHORIONIC GONADOTROPHIN
Authors: Hipkin L. J.
Published: December 2008

The activity of human chorionic gonadotrophin (HCG) in the mouse uterus assay depends on the secretion of endogenous gonadotrophin. This source of gonadotrophin is suppressed when the animals are starved or injected with toxic substances, and the response to HCG is therefore inhibited. There is good evidence that this is the mode of action of the urinary gonadotrophin inhibitor (GIM). Since it has been claimed that stress-induced inhibition of gonadotrophin secretion is related to alterations in adrenocortical function, the present investigation is concerned with the response to HCG in animals with experimental hyper- and hypoadrenocorticalism.

ACTH gel (300 mU) and a depot form of synthetic ACTH (15 μg) augmented the uterine weight response to HCG (0.5 IU). Normal responses were obtained in animals treated with HCG and either cortisol (300 μg), corticosterone (300 μg) or dehydroepiandrosterone (300 μg). Bilateral adrenalectomy produced similar effects to those previously described for GIM and stressful stimuli, namely, inhibition of HCG activity but no impairment of the responses to follicle-stimulating hormone (FSH), HCG given with FSH, or oestrone. It was thought that these results were produced by the metabolic and traumatic effects of the operation rather than by increased secretion of ACTH per se.

Cortisol, corticosterone and ACTH gel did not influence the effect of GIM on HCG activity in the mouse uterus assay.

The results suggest that suppression of endogenous gonadotrophin secretion following acute stress is not secondary to increased secretion of ACTH or hyperfunction of the adrenal cortex.
PLASMA AND URINARY ANDROGENS IN HIRSUTE WOMEN DURING ADRENAL AND OVARIAN SUPPRESSION
Authors: Aakvaag Asbjørn , Vogt Jørgen H. , Fylling Petter
Published: December 2008

Plasma testosterone and urinary androsterone, aetiocholanolone and dehydroepiandrosterone have been estimated in hirsute women with oligoor amenorrhoea. The plasma testosterone in 21 hirsute patients was increased, i.e. 0.117 ± 0.004 (sem) μg/100 ml as compared with the value in normal women, 0.051 ± 0.004. One third of the patients had plasma testosterone values within normal limits. Normal women showed no significant variation throughout the menstrual cycle. Suppression of ovarian function with ethinyloestradiol, 0.60 mg daily for 6 days, reduced the plasma testosterone and urinary androsterone and aetiocholanolone by 27 and 28% respectively. The reduction was statistically significant at the 98 and 99.9% level. Dexamethasone treatment for 2 days with 2 mg daily resulted in a 75% reduction in androsterone and aetiocholanolone excretion and a 30% reduction in plasma testosterone. Combined treatment brought about a 46 and 74% reduction in plasma testosterone and urinary androgens respectively. Dexamethasone administration almost completely removed dehydroepiandrosterone from the urine, whereas a 38% increase in urinary excretion of this steroid was observed during oestrogen administration. This increase was not statistically significant.
TYROSINE AND FREE THYROXINE IN CEREBROSPINAL FLUID IN THYROID DISEASE
Authors: Siersbæk-Nielsen K. , Hansen J. Mølholm
Published: December 2008

Tyrosine and free thyroxine in the CSF and in serum has been measured in 24 euthyroid patients, in 11 patients with thyrotoxicosis and in 4 patients suffering from myxoedema. The thyrotoxic patients had elevated tyrosine levels in the CSF and in the serum, but rise in tyrosine was greater in the CSF than in the serum and the mean ratio CSF tyrosine/serum tyrosine was significantly elevated as compared to the euthyroid group. In the hypothyroid group, in spite of decreased serum tyrosine values the CSF tyrosine was not decreased. Free thyroxine in the CSF was elevated in the thyrotoxic patients and decreased in the hypothyroid patients. In euthyroid, hyperthyroid and hypothyroid patients an equilibrium was found between free thyroxine in the CSF and in the serum. No correlation was found within the groups between the individual values of tyrosine in the serum and in the CSF or between tyrosine and free thyroxine in the serum and in the CSF.
INHERITED DECREASE OF THE BINDING CAPACITY OF THYROXINE-BINDING GLOBULIN (TBG)
Authors: Heinonen O. P. , Lamberg B.-A. , Virtamo J.
Published: December 2008

A family with a decrease in the binding capacity of thyroxine binding globulin (TBG) is described. The gene was probably transmitted by a female who married twice. Five subjects were considered TBG deficient, with TBG values ranging from 8.4 to 16.8 μg/100 ml. Of these subjects 2 were males and 3 females; the males had the lowest binding capacities. In addition, 1 male and 3 females had TBG values within the low normal range and were considered as possibly affected. The mode of inheritance could not be exactly defined but there were indications that it might be an autosomal dominant. The correlation of TBG to the protein-bound iodine in the serum (PBI), to the triiodothyronine uptake by Sephadex (T3-U), to the ratio between them (T3-U/PBI), and to the proportionate free thyroxine (PFT4) was strongly positive or negative. A gradual change in these variables from the affected to the unaffected subjects was observed. These correlations indicated that in normal subjects TBG is the most important factor governing the PBI and free thyroxine levels. In addition, a strong inverse and statistically significant correlation was observed between the binding capacity of TBG and that of the pre-albumin (TPBA). The difference between affected and unaffected subjects with regard to TPBA was also statistically significant.
GONADAL HISTOLOGY IN CHILDREN WITH MALE PSEUDOHERMAPHRODITISM AND MIXED GONADAL DYSGENESIS
Authors: Salle B. , Hedinger Chr.
Published: December 2008

The authors studied the gonads of 20 children presenting different types of pseudohermaphroditism with the object of comparing the histological findings with those observed in cases of simple cryptorchidism. The picture seen in:

Miscellaneous male pseudohermaphroditism is identical to that of simple cryptorchidism.

The feminizing testicular syndrome shows a distinct difference from that seen in the undescended testis of children of the same age. There is proliferation of spindle cells resembling ovarian stroma, but with no follicular derivatives. After puberty there is a discrepancy between the presence of large groups of Leydig cells and an immaturity of the seminiferous tubules.

The testicular lesion in mixed gonadal dysgenesis resembles that of cryptorchidism. However, serial sectioning of entire streaks allowed the demonstration in 3 cases of a tumour entirely composed of germinal cells. In one of these cases a biopsy taken one year previously had revealed no abnormalities. The tumour somewhat resembles a gonadoblastoma but with a difference. No previous reference to such a tumour in children at puberty has been found. Similar lesions were seen in the opposite testicle in two cases. In the light of these findings, it is considered that in such cases the streak and also the testicle should be completely removed to avoid a possible later development of a generalised seminoma.
BIODYNAMICS OF 1.2α-METHYLENE-6-CHLORO-PREGNA-4,6-DIEN-17α-OL-3,20-DIONE (CYPROTERONE) IN MAN FOLLOWING ORAL AND INTRAVENOUS ADMINISTRATION
Authors: Gerhards E. , Röpke H. , Schulze P. E. , Hitze H.
Published: December 2008

The metabolism and pharmacokinetics (biodynamics) of 1,2α-methylene-[14C]-6-chloro-pregna-4,6-dien-17α-ol-3,20-dione (Cyproterone; Cy) have been investigated in man following intravenous and oral administration.

The principal metabolite in the plasma following the intravenous and oral administration is 1,2α-methylene-6-chloro-pregna-4,6-diene-17α,20α-diol-3-one (20α-OH-Cy). After a single oral dose of 100 mg Cy, the concentration of unchanged free Cy during the first 24 hours is about 1 μg/100 ml plasma.

Of 100 mg Cy administered p. o., only about 40% was absorbed, 60% being eliminated in the faeces. In the urine, 20α-OH-Cy and 1,2α-methylene-6-chloro-androst-4,6-diene-3,17-dione(17-keto-Cy) were isolated and identified as the principal metabolites.

About 60% of the radioactivity in the urine, following oral and intravenous administration of [14C]-Cy, is present in the form of watersoluble compounds (conjugates) which cannot be decomposed either with enzymes (β-glucuronidase, sulphatase) or by means of cold or hot acid hydrolysis. Decomposition by solvolysis with perchloric acid in ethyl acetate, however, is quantitative.

On the basis of simulation performed with an analogue computer, the elimination half-life of the deep compartments following intravenous or oral administration of Cy would be between 3 and 5 days, on the basis of 14C-activity. 'Oral administration' of 100 mg Cy daily, as simulated on the analogue computer, is cumulative; an equilibrium in the deep compartment being reached only after about 28 days and that in the blood after about 14 days.