bluuebunny/crossref_metadata_2025 huggingface dataset:
STIMULATION OF LONGITUDINAL BONE GROWTH BY HYPOPHYSEAL HORMONES IN THE HYPOPHYSECTOMIZED RAT
Authors: Thorngren K.-G. , Hansson L. I.
Published: December 2008

The stimulating effect of different pituitary hormones on longitudinal bone growth was determined with tetracycline as intravital marker in hypophysectomized rats. Growth hormone was found to be the most effective growth stimulating pituitary hormone. At considerably higher doses, thyrotrophic hormone (TSH) and prolactin also showed growth stimulating activity. TSH exerts its effect via the production of thyroxine, whereas the growth stimulation by prolactin seems to be a direct effect of this hormone, similar to the effect of growth hormone. The LH, FSH, ACTH, MSH, vasopressin and oxytocin preparations did not stimulate longitudinal bone growth.
OUTCOME OF LONG-TERM ANTITHYROID TREATMENT OF GRAVES' DISEASE IN RELATION TO IODINE INTAKE
Authors: Lumholtz I. B. , Poulsen D. Loldrup , Siersbœk-Nielsen K. , Friis Th. , Rogowski P. , Kirkegaard C. , Hansen J. Mølholm
Published: December 2008

Seventy-seven patients with Graves' disease, with an average of 56 years of age were treated with carbimazole in the period 1968–1975. The duration of therapy was on an average, 17.9 months and the follow-up on an average, 28.5 months. Remission was found only in 32 % of the patients. Data on the urinary iodine excretion from a total of 127 euthyroid controls and 15 patients with Graves' disease living in the same area were collected during the periods: 1962–1964, 1965–1968, 1971–1973 and 1972–1974. No significant difference was found in the urinary iodine excretion in the period 1962–1973 and no significant difference was found in the urinary iodine excretion between the patients with Graves' disease and the euthyroid controls. Our data demonstrate a high relapse rate following long-term treatment with anti-thyroid drugs in an area with relative low iodine intake.
DECREASED PARATHYROID FUNCTION IN HYPERTHYROIDISM: INTERRELATIONSHIPS BETWEEN SERUM PARATHYROID HORMONE, CALCIUM-PHOSPHORUS METABOLISM AND THYROID FUNCTION
Authors: Mosekilde Leif , Christensen Merete Sanvig
Published: December 2008

Serum immunoreactive parathyroid hormone (S-iPTH) was measured together with serum and urinary calcium and phosphorus in 45 hyperthyroid patients in order to assess parathyroid function. Serum calcium and phosphorus were increased and positively correlated to the degree of hyperthyroidism. The prevalence of hypercalcaemia was 51.1 % using serum calcium values corrected for individual variations in serum albumin concentration compared to 15.6% using the uncorrected calcium values. S-iPTH was decreased and inversely correlated to serum calcium (corrected). Subnormal levels of S-iPTH were found in 28.9 % of the patients. The urinary excretion of calcium and phosphorus was increased and positively correlated to the degree of hyperthyroidism. The tubular reabsorption of calcium (TRCa %) was decreased, positively correlated to S-iPTH and inversely correlated to serum calcium. Increased mobilisation of bone mineral in hyperthyroidism is suggested mainly to be responsible for the elevated serum levels and increased urinary excretion of calcium and phosphorus and for the decreased parathyroid function.
VASOACTIVE INTESTINAL PEPTIDE (VIP): VARIATION OF THE JEJUNO-ILEAL CONTENT IN THE DEVELOPING RAT AS MEASURED BY RADIORECEPTORASSAY
Authors: Laburthe M. , Bataille D. , Rosselin G.
Published: December 2008

This study was undertaken to investigate the variations of the Vasoactive Intestinal Peptide (VIP) content of rat jejuno-ileum (JI) with age. VIP was measured by its ability to inhibit competitively the binding of [125I]pork VIP (pVIP) to rat liver plasma membranes. The radio receptor assay was sensitive to 0.5 ng/ml. VIP fragments 1–6, 14–28 and 18–28 exhibited no cross reaction with [125I]pVIP. Glucagon had no effect and secretin was about 100 times less effective than pVIP. Rat VIP was extracted from JI by 0.5 m acetic acid and partially purified by adsorption on silicate. The effect of JI extracts in inhibiting the binding of [125I]pVIP paralleled that of pVIP used as standard. The VIP content of JI showed a 340-fold increase between day 21 post coitum (p.c.): 41 ± 4 ng/JI and day 63 post partum (p. p.): 14 110 ± 954 ng/JI. On a gut weight basis, VIP increased slightly from day 21 p. c. (591 ± 51 ng/g of JI) to day 14 p. p. (906 ± 109 ng/g of JI) and then increased more sharply (day 21 p. p.: 1508 ± 222 ng/g of JI) until day 63 p. p. (2672 ± 207 ng/g of JI). The VIP content seemed to reach a plateau after 2 months. A similar pattern was observed when the results were expressed per mg of JI protein. It is speculated that the rise in VIP content is related to the role of this peptide in the regulation of the gastro-intestinal function and/or the distribution of fuels in the organism.
SERUM CORTISOL APPEARANCE-DISAPPEARANCE IN ADRENAL INSUFFICIENCY AFTER ORAL CORTISONE ACETATE
Authors: Barbato Anthony L. , Landau Richard L.
Published: December 2008

Six patients with long-standing idiopathic primary adrenal insufficiency were given 25 mg of cortisone acetate orally on two occasions. Circulating serum cortisol levels were determined hourly for five hours after ingestion. Two patients were additionally studied with an oral dose of 20 mg of cortisol. Marked patient to patient variation in peak hormone and in fifth hour hormone levels was observed. Both values were lowest in the two chronically symptomatic patients who had been maintained on empiric glucocorticoid replacement. Specific information on blood cortisol levels in treated Addisonian individuals has not been previously reported.
STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE
Authors: Landgren B.-M. , Aedo A.-R. , Nuñez M. , Cekan S. Z. , Diczfalusy E.
Published: December 2008

By the use of a non-thrombogenic pump, blood was withdrawn continuously at a rate of 4.0 ml/h over a period of 48 h from 10 normally menstruating women during various phases of the peri-ovulatory period and the integrated levels of oestradiol, oestrone, 17-hydroxyprogesterone, progesterone, 20α-dihydroprogesterone and biologically active luteinizing hormone (LH) were estimated in 3-hourly plasma collections.

The first significant change detected two days prior to the LH surge (day LH-2) in one subject studied during this period was a continuous parallel rise in oestradiol and oestrone levels, which occurred in the absence of any simultaneous change in LH and 17-hydroxyprogesterone levels.

Marked fluctuations followed by a sudden drop in oestradiol levels were observed in another woman during the day preceding the LH peak (day LH-1). These changes were not associated with similar alterations in oestrone levels. The marked drop in oestradiol coincided with the beginning of a simultaneous major rise in LH and 17-hydroxyprogesterone levels followed some 6 to 9 h later by a small but significant increase in progesterone levels.

The period of the LH surge (day LH) was studied in 3 women. This period was characterised by a constant decline in oestradiol levels in the presence of unchanged oestrone values. The decrease in oestradiol levels preceded the LH peak by at least 12 h. The LH peak was biphasic in all subjects; both the ascending and descending limbs of it were significantly correlated to similarly changing levels of 17-hydroxyprogesterone. The increase in these two hormones preceded that in progesterone levels, which occurred later, at the time of the steepest rise in LH levels. The findings of the subsequent day (day LH+1) were characterised in two subjects by a parallel decrease in plasma oestradiol, LH and 17-hydroxyprogesterone levels, until a plateau was reached. This plateau coincided with a new rise in progesterone and 20α-dihydroprogesterone levels.

The hormonal profile observed two days following the LH surge (day LH + 2) in 3 women was similar to that of the preceding day, with the exception of a beginning new rise in 17-hydroxyprogesterone levels by the end of day LH + 2. This second rise in 17-hydroxyprogesterone paralleled that in progesterone and 20α-dihydroprogesterone levels and occurred in the presence of decreasing levels of LH.

The data reported strongly suggest that different control mechanisms are involved in the regulation of ovarian steroid secretion during the various phases of the peri-ovulatory period.
FOETAL AND MATERNAL HORMONAL CHANGES PRECEDING NORMAL BOVINE PARTURITION
Authors: Hunter J. T. , Fairclough R. J. , Peterson A. J. , Welch R. A. S.
Published: December 2008

Successful chronic cannulation of the foetal posterior vena cava and maternal utero-ovarian and jugular veins in five Jersey cows between days 240 and 260 of gestation enabled changes in plasma hormone levels preceding calving to be monitored. All cows delivered live calves within the expected range of gestation for the breed.

Corticosteroids were assayed by competitive protein-binding, and prostaglandin F, progesterone, oestrone and oestradiol-17β by radioimmunoassay. Foetal corticosteroids rose slowly from 5.0 ± 0.7 ng/ml at 20 days to 9.3 ± 3.0 ng/ml at 10 days before term, then progressively increased to a mean of 74 ng/ml at calving. Maternal levels remained relatively constant at 5 to 15 ng/ml, though higher concentrations occurred following surgery. Foetal oestrone and oestradiol-17β concentrations were both less than 50 pg/ml and showed little change toward term. The maternal uteroovarian oestrogens increased slowly from 20 to 10 days pre-partum and then rose more rapidly reaching peak levels (2.9 ± 0.6 ng/ml for oestrone and 1.4 ± 0.3 ng/ml for oestradiol-17β) 1 to 4 days before delivery. Maternal progesterone concentrations fell towards term, with a rapid decrease over the last 36–48 h. Prostaglandin F levels showed little change until 36–48 h before calving when they gradually increased until the last 24 h where was a dramatic rise, reaching peak levels (5.7 ± 0.6 ng/ml) during labour.
BIOLOGICALLY ACTIVE LUTEINIZING HORMONE (LH) IN PLASMA: II. COMPARISON WITH IMMUNOLOGICALLY ACTIVE LH LEVELS THROUGHOUT THE HUMAN MENSTRUAL CYCLE
Authors: Romaní P. , Robertson D. M. , Diczfalusy E.
Published: December 2008

The levels of biologically active luteinizing hormone were determined by an in vitro bioassay method in plasma samples collected daily over a complete menstrual cycle from 12 menstruating women. These cycles were normal according to a number of criteria, including daily plasma levels of oestradiol, 17-hydroxyprogesterone and progesterone.

Immunoreactive LH was estimated in the same 12 cycles by a radioimmunoassay (RIA) procedure (HCG-RIA) using an HCG antiserum and iodinated HCG. The 2nd IRP of HMG was selected as standard although significant deviations from parallelism were found with 7 out of the 12 plasma pools studied. The use of the 1st IRP of human pituitary gonadotrophins (FSH and LH (ICSH)) for bioassay (hereafter HPG-1st IRP) as standard in this system resulted invariably in invalid assays, due to lack of parallelism.

Immunoreactive LH was also measured in 8 of the 12 cycles by a RIA procedure (HLH-RIA) using a human LH antiserum and iodinated human LH of pituitary origin. Results are expressed in terms of the HPG-1st IRP.

The plasma levels of biologically and immunologically active LH were qualitatively similar throughout the menstrual cycle. However, the LH levels measured by the bioassay invariably exceeded those estimated by the RIA procedures. The biological to immunological (B/I) ratio over the entire menstrual cycle (312 comparisons) was 5.5 with 95% confidence limits at 5.2 and 5.8 when the HCG-RIA system was employed. Using the HLH-RIA system (208 comparisons), the corresponding ratio was 6.4 (6.0:6.9).

When regression lines were calculated using the bioassay results as the independent variable and the RIA results as the dependent variable, the 95% confidence limits of the regression lines did not include the origin. Furthermore, in keeping with the high B/I ratios, the slopes of the two regression lines and their confidence limits differed markedly from unity. It is concluded that although qualitatively similar profiles were observed between the biological and immunological activities throughout the menstrual cycle, two aspects require further attention. Firstly, the elevated B/I ratios together with the behaviour of the dose-effect lines obtained with different standards in the various RIA systems suggest that presently available reference standard preparations of pituitary and/or urinary origin are not suitable for the assay of LH in human plasma. Secondly, from the regression analyses of the biological and immunological activities it is inferred that the RIA methods detect immunological activity which is not associated with biological activity. If so, the validity of these RIA procedures for specifically measuring low levels of biologically active LH in plasma may be in question.
HYPOGONADISM, GALACTORRHOEA AND HYPER-PROLACTINAEMIA: EVALUATION OF PITUITARY GONADOTROPHINS RESERVE BEFORE AND UNDER BROMOCRIPTINE
Authors: Asfour M. , L'Hermite M. , Hedouin-Quincampoix M. , Fossati P.
Published: December 2008

Twenty patients with hypogonadism (19 women with amenorrhoea and 1 man with impotence and infertility), galactorrhoea and hyper-prolactinaemia (range: 36 to 344 ng/ml) were studied. The radiological study of the sella turcica, including in all cases hypocycloidal tomograms, allowed classification of the patients into 3 groups: group I (n = 4) had a grossly enlarged sella turcica, group II (n = 12) had localized alterations indicating the probable existence of a prolactin-secreting microadenoma ("microdeformation") while group III patients presented no radiological abnormality.

Before treatment, all the patients were submitted to a complete evaluation of the function of their anterior pituitary, including the LH and FSH responses to iv administration of Gn-RH. All the group I patients had low basal LH levels and a blunted response to Gn-RH. The basal LH and in response to Gn-RH were normal in most of the group II patients and in all of the group III patients. An exaggerated FSH response to Gn-RH was observed in 6/12 patients with microdeformation (group II) but not in groups I and III patients. A low LH and a blunted LH response to Gn-RH is highly suggestive of the existence of a pituitary prolactin-secreting adenoma in case of amenorrhoea and hyper-prolactinaemia patients; a normal response does not however rule out such a diagnosis. The reasons for an exaggerated FSH response to Gn-RH in patients with suspected prolactin-secreting microadenoma remain to be investigated though this pattern can also occur in other cases of amenorrhoea. Hence the Gn-RH test might contribute to the assessment of the hypothalamo-pituitary axis of patients with hyper-prolactinaemia.

Six patients treated for 4 months with bromocriptine (CB-154) were submitted to re-evaluation of their pituitary gonadotrophins reserve. All the women experienced restoration of menses with 39 days of treatment and the male patient regained potency. It was observed that bromocriptine treatment and subsequent normalized prolactin levels in the 4 group II women tested were associated with normalization of their previously exaggerated FSH response to Gn-RH; LH responses were also diminished in these cases. These data are compatible with the hypothesis that hyper-prolactinaemia per se could interfere with the endogenous secretion of Gn-RH at the hypothalamic level. In one patient with grossly enlarged sella turcica and a previous lack of an LH and FSH response to Gn-RH, bromocriptine treatment restored a normal gonadotrophins response, confirming that, in this case, the alteration of this response was indeed due to a prolonged lack of endogenous Gn-RH secretion.
EFFECTS OF CHRONIC RENAL DISEASE ON THYROID HORMONE METABOLISM
Authors: Finucane J. F. , Griffiths R. S. , Black E. G. , Hall C. L.
Published: December 2008

Serum concentrations of total and free thyroxine and triiodothyronine together with urine losses of unconjugated thyroid hormones have been measured in normal subjects and in patients with renal disease. Serum total hormone values in the hypothyroid range were common in the renal group and correlated inversely with the degree of renal impairment but not with renal loss of hormone which in the case of thyroxine exceeded the average normal daily loss ten-fold. The euthyroid state of patients with renal disease was best reflected by serum free thyroxine concentration which in every case was within the normal range.

Poor correlation was apparent between the respective urine concentrations of albumin and thyroxine, and the reasons for this are discussed.
PROTEIN CONCENTRATION OF THE RAT THYROID COLLOID DURING THYROXINE TREATMENT
Authors: Smeds S. , Ekholm R. , Ericson L. E.
Published: December 2008

Sprague-Dawley rats were given daily doses of 20 μg thyroxine for varying periods between 1 and 21 days. Samples of colloid were obtained by micropuncture in vivo of follicles in the thyroid isthmus. The protein content of the samples was determined by gel electrophoresis and the volume by a technique based on radioactivity measurement. The relative volume of the follicle lumina was determined by light microscopy.

Treatment with thyroxine resulted in an increase in the protein concentration of the colloid. This increase was statistically significant after 2 days and the concentration remained elevated throughout the experimental period. The size of the follicle lumina also increased, most rapidly during the first week.

It is suggeted that the increase in protein concentration of the colloid during thyroxine treatment is due to inhibition of endocytosis of colloid in combination with the discharge into the follicle lumen of highly concentrated protein.
ENDOCRINE AND REPRODUCTIVE REPERCUSSIONS OF IMMUNIZATION AGAINST PROGESTERONE AND OESTRADIOL IN FEMALE RATS
Authors: Kaushansky A. , Bauminger S. , Koch Y. , Lindner H. R.
Published: December 2008

Mature female rats were immunized with BSA-conjugates of oestradiol17β-6-carboxymethyloxime or progesterone-11-hemisuccinate. Sera tested two months later at 1/2000 dilution bound 63.3 % ± 3.1 sem and 21.2% ± 2.3 of the homologous tritiated hormone (10 pg), - oestradiol-17β (Oe2) and progesterone (P), respectively. Rats immunized against Oe2 had a significantly longer oestrous cycle (8.2 days vs. 4.5 days in BSA-immunized rats), with a prolonged leukocytic phase. The cycle of rats immunized against P was also prolonged (10.5 days), but in this group the cornified smear phase was abnormally extended. The luteinizing hormone (LH) normally observed on the afternoon of pro-oestrus failed to occur in the rats immunized against Oe2 and in 70 % of rats immunized against P. The latter animals, however, showed sporadic LH discharges during periods of persistent cornification. Immunization against P resulted in elevated total (free plus bound) plasma P levels; immunization against Oe2 prevented the pro-oestrous rise in plasma P. Mating of rats immunized against Oe2 resulted in normal pregnancies, while none of the rats immunized against P delivered.
HUMAN TESTOSTERONE-OESTRADIOL BINDING GLOBULIN IN HEALTH AND DISEASE
Authors: Wenn R. V. , Kamberi I. A. , Vossough P. , Kariminejad M. H. , Torabee E. , Ayoughi F. , Keyvanjah M. , Sarberi N.
Published: December 2008

Levels of testosterone-oestradiol binding globulin (TeBG) were measured by a precipitation technique in terms of dihydrotestosterone-5α (DHT) binding capacity in children, adult males and females, pregnant and hirsute women and women with various trophoblastic disorders. It was found that TeBG levels in children of either sex (1.92 ± 0.16 μg DHT bound/100 ml serum) approached the normal female range (2.31 ± 0.11) and were distinctly higher than those of the adult male (1.04 ± 0.09). In both pregnancy and trophoblastic disease (hydatidiform mole and choriocarcinoma but not metastatic choriocarcinoma) TeBG levels were elevated (17.5 ± 0.70 and 14.9 ± 1.49, respectively). In hirsutism TeBG was depressed (1.17 ± 0.09) and comparable with the levels in normal male subjects. A number of other parameters, HCG, oestradiol-17β, testosterone and progesterone were measured and found to be similar to those previously reported in the literature. It appears that TeBG titre might provide an additional index in following the prognosis of trophoblastic disorders, besides HCG measurement.
ESTERASE XXV
Authors: Deimling O. v. , Riebschläger M.
Published: December 2008

The Es-9 esterase is expressed in the cortical zone of the NMRI mouse kidney only in the presence of testosterone. In disc electrophoresis, three esterase bands, absent in the control, emerge under the influence of exogenous testosterone, accompanied by the appearance of active sites, as shown by marking with [3H]diisopropyl fluorophosphate ([3H]DFP). It is suggested that the testosterone dependent appearance of Es-9 activity is due to true enzyme induction which requires the presence of an intact testosterone receptor.
INDIRECT EVIDENCES OF PROLACTIN INVOLVEMENT IN PRECOCIOUS PUBERTY INDUCED BY HYPOTHALAMIC LESIONS IN FEMALE RATS
Authors: Alvarez E. O. , Hancke J. L. , Advis J. P.
Published: December 2008

The effects of 2-bromo-α-ergocryptine (CB-154) administration in maturing female rats with precocious puberty induced by hypothalamic lesions, as well as the milk secretion rate in these animals after their first parturition were studied.

Treatment with CB-154 inhibited precocious vaginal opening induced by hypothalamic lesions. After the treatment with the derivative was terminated, the ovulatory response was not different from that of intact control rats. After their first parturition lesioned rats accumulate milk at a faster rate, following an initial depletion period, than their non-operated controls.

These results suggest than an alteration in prolactin release may be involved in determining the precocious puberty induced by lesions of the anterior hypothalamic area.
A COMPARATIVE STUDY OF IODINE UPTAKE BY THYROID AND THYMUS GLANDS OF MALE AND FEMALE SPRAGUE-DAWLEY RATS OF DIFFERENT AGES
Authors: Goldman Max , Bauer Stephen R.
Published: December 2008

The iodine concentrating ability of thyroid glands, thymus gland and skin in Sprague-Dawley rats was assessed by determining the tissue/blood radioiodide concentration ratios. Tissue/blood ratios are significantly affected by the age of the rats, however, thymus/blood radioiodide ratios never exceeded unity. The comparative uptake of 131I by thymus and thyroid tissue expressed as thymus/thyroid (%) for neonate animals was 10–16 times greater than those obtained for older rats. Moreover, the fraction of injected dose of radioiodide in thymus tissue never exceeded that of the thyroid or skin, and paralleled the concentration of radio-activity in the blood. These results indicate that although neonate thymus tissue contains a significantly greater amount of radioactivity than the thymus of older rats, an active iodide concentration mechanism is not involved.
RAT ENDOMETRIUM ENZYMES IN 4-DAY OESTROUS CYCLE AND EARLY PREGNANCY
Authors: Jelínek Jan , Jelínková Marta
Published: December 2008

The specific activities of lactate dehydrogenase (LDH) and its M-type (M-LDH), β-glucuronidase (β-GR), acid phosphatase (ACP) and alkaline phosphatase (AP) were determined. The specific activities of the enzymes (LDH, β-GR) in the myometrium were lower and their changes less pronounced than in the endometrium. We, therefore, determined the enzymes in the rat endometrium only in further experiments.

All enzymes react sensitively to the changes induced in the endometrium by endogenous hormones in the course of a 4-day cycle: pro-oestrus (P) is characterized by rather low enzyme activities, oestrus (E) by a peak of LDH and M-LDH and a rise of AP. In metoestrus (M) there is a peak of β-GR, ACP and AP. Dioestrus (D) is characterized by a significant decrease in LDH and M-LDH and by elevated values of all the other enzymes.

The values on the individual days of the 4–day cycle were compared with days 4–6 of pregnancy. The reason for this was that if the rats were not mated, they would, respectively, return to pro-oestrus instead of being 4 days pregnant, to oestrus instead of being 5 days pregnant, or to metoestrus instead of being 6 days pregnant.

We found the following differences: on day 4 of pregnancy LDH and M-LDH were lower and ACP and AP higher than in P. On day 5 of pregnancy the LDH, M-LDH, β-GR and AP were lower than in E On day 6 of pregnancy the LDH, M-LDH, ACP and especially β-GR, were lower than in M.
PITUITARY GONADOTROPHIN SECRETION DURING THE FIRST WEEKS OF PREGNANCY
Authors: Jeppsson Sten , Rannevik Gunnar , Thorell Jan I.
Published: December 2008

A longitudinal study of basal plasma LH and FSH and their responses to 25 μg LRH iv as well as basal levels of oestradiol, progesterone, prolactin and HCG was performed every week in 3 women, pregnant after heterologous insemination, from conception until the 6th week of gestation. A comparative study was carried out in 7 women in cycles in which no conception occurred after insemination. All hormones were assayed with radioimmunoassay. LH was measured with a specific assay for native LH, which did not cross-react with HCG.

A decrease in basal levels of LH and FSH as well as decreasing responses to LRH was found during the first 2 weeks of gestation. These changes did not differ from what was observed during the luteal phase in the non-conception cycles. One week later the basal FSH levels and the FSH response in the pregnant women showed a further decrease, while in the non-pregnant women, now reaching the early follicular phase, a rise in FSH basal levels occurred. The basal levels of LH and the LH response, however, did not differ from that found in the nonpregnant women at this time.

FSH basal levels remained below the lower normal limit in eumenorrhoic women from the 3rd week of gestation. By this time the FSH response was almost completely inhibited. The LH basal levels, however, remained above the lower normal limit in eumenorrhoic women, but the LH response to LRH progressively decreased and was completely inhibited by the 5th week of gestation.

In the non-conception cycles the LH response varied with the levels of oestradiol in plasma. This was not found in the pregnant women as the decrease in gonadotrophin response occurred while oestradiol remained at mid-cycle levels during the first 4 weeks of gestation. Rather it seems that the increasing and continuously elevated level of progesterone, in the presence of appropriate levels of oestradiol, might be the main go nadal steroid responsible for the diminishing pituitary secretion.

The contribution of HCG to the further decrease in gonadotrophin secretion after the 2nd week of pregnancy cannot be answered by the present studies.

Prolactin remained at non-pregnant levels until the 6th week of gestation, and appeared to have no influence on the secretion of gonadotrophins during early pregnancy.
A SIMPLE AND RAPID METHOD TO MEASURE NON-PROTEIN-BOUND FRACTIONS OF CORTISOL, TESTOSTERONE AND OESTRADIOL BY EQUILIBRIUM DIALYSIS: COMPARISON WITH CENTRIFUGAL FILTRATION
Authors: Kley H. K. , Bartmann E. , Krüskemper H. L.
Published: December 2008

A simple method for measuring the free, non-protein-bound steroid fraction in plasma by equilibrium dialysis is described. The alteration occurring in the volume of the inner phase (undiluted plasma) is corrected by the difference in weight before and after dialysis. Total cortisol was determined by radioimmunoassay. Although it is not possible to differentiate between values for total cortisol after ACTH stimulation (242.2 ± shing's syndrome (n: 15)) and women treated with oestrogens (211.8 ± 42.0 ng/ml (n: 20)), there were significant differences for free cortisol (ACTH stimulation: 29.3 ± 5.6 ng/ml; Cushing's syndrome: 31.5 ± 8.6 ng/ml; women under increased oestrogenic activity: 10.0 ± 2.1 ng/ml; pregnant women: 13.7 ± 5.1 ng/ml plasma). Compared with normal values for healthy women and men (9.3 ± 1.4 ng/ml), women with increased oestrogenic activity showed slight elevations of free cortisol. Compared to cortisol, the percentage of dialysable testosterone and oestradiol was lower in women than in men (1.57 vs. 2.08% for testosterone and 1.68 vs. 2.15% for oestradiol). In healthy men the concentration of free steroid was 13.1 ± 1.0 ng free testosterone/100 ml plasma (0.44 ± 0.045 pg free oestradiol/ml plasma), in healthy women 0.64 ± 0.07 ng/100 ml (0.98 ± 0.10 pg/ml) and in women receiving oestrogens 0.37 ± 0.04 ng/100 ml (0.01 ± 0.015 pg/ml). When the method described here for determining the free fractions of cortisol (n: 45), oestradiol (n: 18) and testosterone (n: 18) at 37°C is compared with the method of centrifugal filtration, the correlation was r: 0.80, r: 0.86 and r: 0.91, respectively. In practice, equilibrium dialysis with undiluted plasma is simple, fast and can be applied to all steroid hormones. It allows direct measurements of non-protein-bound steroids under nearly physiological conditions.
LONG-TERM TREATMENT WITH 2—Br—α—ERGOCRYPTINE IN ACROMEGALY
Authors: Belforte L. , Camanni F. , Chiodini P. G. , Liuzzi A. , Massara F. , Molinatti G. M. , Müller E. E. , Silvestrini F.
Published: December 2008

Thirty acromegalic subjects underwent chronic CB154 therapy (10–20 mg daily) for periods ranging from 3 months up to 2 years. In 18 out of 21 patients, who exhibited consistent HGH reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50 % of base line values, e.g. from mean daily values between 14–197 ng/ml (mean ± sem = 57.8 ± 12.4 ng/ml pre-treatment) to 2–19 ng/ml (mean 8.3 ± 1.2 ng/ml post-treatment). In 12 of the subjects who responsed to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidenced with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH or insulin-induced GH release.

These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g. reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma phosphorus after insulin, decreased urinary excretion of phosphate, hyper hydroxyprolinuria and hyper-calciuria. Collectively, these data demonstrate that CB154 thrapy is effective in reducing HGH hyper-secretion in many acromegalic patients during long-term treatment.
ANALYSIS OF DIAMETERS OF HUMAN PITUITARY HORMONE SECRETORY GRANULES
Authors: Gray A. B.
Published: December 2008

Measurements were made on electron micrographs of six human anterior pituitary glands of the maximal diameters of secretory granules in 130 cells, average 91 granules per cell. This was done in an attempt to classify the various hormone types solely by differences in the mean diameters of the secretory granules. The range of diameters in nanometers could be segregated into six subgroups of the following suggested functions: 135.5 ± 13.6 TSH, 181.6 ± 9.3 LH, 226.0 ± 19.4 FSH, 356.8 ± 30.5 ACTH/MSH, 452.9 ± 23.8 GH, 559.9 ± 38.0 prolactin.
THYROID HORMONE-BINDING INTERACTIONS IN CYTOSOL OF RAT ANTERIOR PITUITARY
Authors: Galton Valerie Anne
Published: December 2008

Thyroxine (T4) and triiodothyronine (T3)-binding interactions in preparations of rat anterior pituitary gland have been studied. T4 is bound primarily to extranuclear binding sites located in the cytosol fraction of the cell. These sites have a medium affinity for T4: Ka = 2.5 × 108 1/mol and a maximum binding capacity (MBC) of 1.15 pmol/mg tissue (wet weight). Binding of T3 to these sites is minimal. The extent of binding of T4 is influenced by the pH of the system and the temperature of incubation. The relative effectiveness of T4 analogues in displacing bound T4 is tetrac > T4 > triac > D-T4 > T3. Similar T4-binding sites are present in other rat tissues, but in all except serum, binding activity is lower than in the pituitary. T4-binding by serum contaminating the pituitary preparations contributed only partially to the total activity observed. Concomitant assessment of T4-binding activity and T4 metabolism in pituitary homogenates prepared at different pH values indicated an inverse relationship between the two processes. The possible role of thyroid hormone binding in cytosol in influencing the intracellular distribution of thyroid hormones is discussed.
OVARIAN STEROID EFFECTS ON GONADOTROPHIN OUTPUT, AND ON THE INCORPORATION OF 35S FROM METHIONINE INTO PROTEIN OF DISCRETE BRAIN AREAS AND THE ANTERIOR PITUITARY
Authors: ter Haar M. B. , MacKinnon P. C. B.
Published: December 2008

The effects of various ovarian hormones administered on the morning of pro-oestrus on gonadotrophin levels and the incorporation of 35S from methionine into protein of discrete areas of the brain and the anterior pituitary were investigated at 15.00 h of the same day in female rats. The hormones which were investigated in this study could be divided in general into two groups according to their actions. The first group, consisting of oestradiol-17β and progesterone, tended to advance the preovulatory surge of luteinizing hormone (LH) by 3–6 h from 18.00–21.00 h, together with the peaks of [35S] incorporation in the median eminence area and the anterior pituitary which normally accompany the LH surge. The second group, consisting of the LH-stimulated reduced progesterone metabolites, 5α-pregnane-3,20-dione (pregnanedione) and 20α-hydroxypregn-4-en-3-one (dihydroprogesterone), tended to inhibit serum gonadotrophin levels as well as inhibiting the pro-oestrous increase of [35S] incorporation in the median eminence area and in the amygdala, but not in the preoptic area and the anterior pituitary.

On the afternoon of pro-oestrus in intact animals, luteinizing hormonereleasing hormone or LH administration had the same effect on [35S]incorporation in the brain as did the progesterone metabolites, though this effect was not observed if the animals had been ovariectomized a few hours beforehand.

It is suggested that certain ovarian hormones are involved in the neural events which induce the pre-ovulatory LH surge, while others are associated with neural events which terminate the stimulus for the LH surge.
SUBCELLULAR FRACTIONATION BY CENTRIFUGATION OF HOMOGENATES OF THE NEURAL LOBE OF THE BOVINE PITUITARY GLAND: IDENTIFICATION OF DIFFERENT POOLS OF HORMONE IN THE HOMOGENATE AND ISOLATION OF NEUROSECRETOSOMES
Authors: Vilhardt Hans , Baker Ruth V. , Hope Derek B.
Published: December 2008

1. Homogenates of bovine pituitary neural lobe tissue were subjected to differential centrifugation. Six subcellular fractions (I-VI) were obtained and the distribution among them of various cell organelles was studied by means of markers. Fraction II (800–3000 gav), the nerve-ending fraction (neurosecretosomes), contained sedimentable lactate dehydrogenase, hormone and a large proportion of the total Mg2++ Na++ K+-ATPase.

2. Lysis of the neurosecretosomes in hypotonic sucrose solutions led to loss of lactate dehydrogenase and vasopressin.

3. Centrifugation of the granule fraction (IV) on a sucrose gradient (1.3–2.0 m sucrose) gave a bimodal distribution of vasopressin. Purified neurosecretory granules were recovered from the denser band. Centrifugation on modified gradients (0.8–2.0 or 0.4–2.0 m sucrose) increased the yield of hormone in the denser band but the purity of the granules was decreased.

4. Considerable purification of the neurosecretosomes (fraction II) was achieved by "washing". Centrifugation of washed neurosecretosomes on sucrose density gradients led to the accumulation of all activities at a region between 1.4 and 1.5 m sucrose.

5. The distribution of Mg2++ Na++ K+-ATPase in centrifugal fractions indicated that the neurosecretosomes had been isolated in relatively high yield.
SERUM THYROXINE-BINDING GLOBULIN: DETERMINATION BY COMPETITIVE LIGAND-BINDING ASSAY IN THYROID DISEASE AND PREGNANCY
Authors: Mulaisho C. , Utiger R. D.
Published: December 2008

Serum thyroxine-binding globulin (TBG) concentrations were measured by competitive ligand-binding assay in normal subjects and patients with a variety of abnormalities of thyroid hormone production or TBG production. The mean serum TBG concentration in 73 normal adults was 3.4 ± 0.6 mg/100 ml. No correlations with age, sex or serum thyroxine (T4) or triiodothyronine (T3) concentrations were found. Serum TBG concentrations were normal in patients with hyperthyroidism. They were significantly elevated in hypothyroid patients, and fell to normal with thyroxine treatment. In pregnant women, serum TBG concentrations were markedly increased, being 7.1 ± 1.2 (mean ± sd) mg/100 ml in women in their first trimester, 9.0 ± 1.0 mg/100 ml in the second trimester and 8.9 ± 1.6 mg/100 ml in the third trimester. There was a positive correlation between serum TBG concentration and both serum T4 and serum T3 concentrations in pregnant women. Competitive ligand-binding assay is a simple and reliable method for TBG assay and yields results similar to those of electrophoretic saturation techniques.
ENDEMIC GOITRE IN ALTO ADIGE (ITALY)
Authors: Platzer S. , Fill H. , Riccabona G. , Glatzl J. , Seidl J. , Cenderelli G. , Migliardi M. , Varetto H. , Costa A.
Published: December 2008

The whole population of Certosa (Karthaus) (altitude 1327 m), a little village in the Alto Adige province in Northern Italy, was studied regarding the incidence and pathophysiological data of endemic goitre. The study included 204 subjects: in 85 % of the whole population, and in 48 % of the school-children population from 6-14 years of age, thyroid enlargement and/or nodularity was found. The 24 h [131I]uptake was 48.6 ± 11.96; the grade "O" thyroids also showed an increased uptake. The region is poor in iodine; the mean iodine content of 55 samples of local drinking water was 0.81 ± 0.96 μg/I; the iodine content of several foodstuffs was definitely lower than those from Turin's markets. The mean iodine excretion in 60 samples of urine was 35.96 ± 22.4 μg/g creatinine. Urinary iodine excretion showed a linear negative correlation with [131I]uptake and did not correlate well with the presence or size of the goitre.

The mean values of PBI (6.12 ± 1.57 μg/100 ml) of T4 (7 ± 2.3 μg/100 ml), of T3 (121 ± 55.4 ng/100 ml) and of a free thyroxine index (ETR = 0.95), as well as of TSH (2.63 ± 1.9 μU/ml) were in the normal range. Grade III goitres had slightly lower hormonal values, and a somewhat elevated T3/(T4x100) ratio (0.19). Serum TSH levels showed no correlation with the presence or size of the goitre, radioiodine uptake, the urinary iodine excretion, and not always showed an inverse correlation with the peripheral thyroid hormone values. Urinary thiocyanate excretion (mean value 9.28 ± 2.96 mg/24 h) did not show any relation to the presence of goitre.

Raven's tests and physical data obtained from school-children in Alto Adige show some slight alteration in the distribution pattern when compared to normal populations.

It is concluded that iodine deficiency exists in the studied area, but that it is not always associated with goitre, and that other pathological factors must be involved in goitrogenesis. Goitre is not coupled with enhanced TSH serum levels.

The slight alteration in intellectual and somatic development in schoolchildren may possibly be related to iodine deficiency; other environmental or genetic factors, however, cannot be excluded.
C-PEPTIDE IN DIABETIC CHILDREN AFTER STIMULATOIN WITH CLUCAGON COMPARED WITH FASTING C-PEPTIDE LEVELS IN NON-DIABETIC CHILDREN
Authors: Ludvigsson J. , Heding L. G.
Published: December 2008

Fasting serum C-peptide and total immunoreactive insulin (IRI) were determined in 38 non-diabetic children and adolescents 6–22 years old. C-peptide varied between 0.22–0.73 pmol/ml (mean ± sd, 0.45 ± 0.11). There was a tendency to higher values during puberty. No difference was found between subjects with or without a family history for diabetes. IRI varied between 0–31 μU/ml (mean ± sd, 11.3 ± 6.5).

The C-peptide response to glucagon was studied in 10 insulin dependent juvenile diabetics 11–19 years old, who had had measurable amounts of fasting C-peptide on some occasions during the previous years. Duration of diabetes varied between 4–12 years. A slight but significant rise in C-peptide level occurred in 3 patients. Their metabolic control estimated on the basis of daily urinalysis was "excellent" or "good". The results support the hypothesis that even trace remnants of the beta cell function may be of importance for the metabolic control in juvenile diabetes.
STUDIES ON THE MECHANISMS OF SOMATOSTATIN ACTION ON INSULIN RELEASE
Authors: Claro A , Grill V. , Efendić S. , Luft R.
Published: December 2008

The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Concentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mm glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H] cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H] cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H] cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30 %.

It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.
STUDY OF THE EFFECT OF OESTRADIOL ON HEXOSAMINE-CONTAINING SUBSTANCES AND A POSSIBLE RECEPTOR IN THE SKIN OF MALE MICE
Authors: Kanke Y. , Nishina H. , Mori Y. , Bashey R. I.
Published: December 2008

Male mice were treated with 10 μg of oestradiol for 5 days in order to study the effect of the hormone on both the distribution and the rate of synthesis of glycosaminoglycans and glycoproteins in the skin. Oestradiol exerts a very specific effect on glycosaminoglycans by increasing hyaluronic acid concentration more than 11 times. Effects on other hexosaminecontaining substances were much smaller and less consistent. Although the above increase of hyaluronic acid was due mainly to an augmentation of its synthesis, the results also indicate the possibility of a blockage in the breakdown process. Despite the fact that oestrogen produces such large changes, a specific cytosol receptor of the hormone was not discerned and it was concluded that male mouse skin is not an oestrogen receptor tissue in the classical sense.
CONGENITAL GENERALIZED LIPODYSTROPHY AND EXPERIMENTAL LIPOATROPHIC DIABETES IN RABBITS TREATED SUCCESSFULLY WITH FENFLURAMINE
Authors: Trygstad Olav , Foss Irene
Published: December 2008

Lipoatrophic diabetes has been produced in rabbits by injection of a fraction prepared from the urine from patients with congenital generalized lipodystrophy. Both these conditions are considered to be hypothalamic syndromes. The animals, and a patient with congenital generalized lipodystrophy and latent diabetes were treated with the dopamine receptor blocker, pimozide, for 4 and 17 months, respectively. The results were discouraging even though the patient got a daily dose of 16 mg pimozide. Fenfluramine has a lowering effect on brain serotonin, and peripheral effects on glucose and triglyceride metabolism. This drug improved the general condition of the rabbits with lipoatrophic diabetes, as well as that of the patient with congenital generalized lipodystrophy. The rabbits became normoglycaemic and insulin sensitive. In the patient a normalization of the urinary excretion of the serotonin metabolite 5-OH-indole acetic acid was observed.

His voracious hunger and profuse perspiration were reduced, the hyperkeratotic layer of the skin peeled off, and the pigmentations of the skin decreased. There was observed an improvement of ALAT and ASAT, normalization of the fasting blood glucose, and increased sensitivity to exogenous insulin. After 11 months of 200 mg fenfluramine daily addtitional administration of 2 g clofibrate per day produced normalization of the serum triglyceride concentration and a marked reduction of the resistance to insulin. Three more patients with congenital generalized lipodystrophy, two of whom have manifest diabetes, have now started treatment with fenfluramine and are improving. The rabbits got relapse of their lipoatrophic diabetes when the fenfluramine treatment was stopped. It is suggested that a disturbance in the serotonin metabolism of the central nervous system may be of pathogenetic importance in congenital generalized lipodystrophy.
EFFECT OF THYROTROPHIN RELEASING HORMONE (TRH) IN PATIENTS WITH PITUITARY DISORDERS
Authors: Lindholm J. , Dige-Petersen H. , Hummer L. , Rasmussen P. , Korsgaard O.
Published: December 2008

The secretion and biological activity of thyroid stimulating hormone (TSH) were studied in 22 patients with a pituitary tumour (17 acromegalics and 5 patients with a chromophobe adenoma) and in 36 hypophysectomized patients (16 acromegalics and 20 with a chromophobe adenoma). Thyroid function was assessed by serum thyroxine (T4), serum triiodothyronine (T3), and thyroxine-binding globulin (TBG) concentration. Serum TSH was measured before and after injection of TSH releasing hormone (TRH), and in 19 hypophysectomized patients the T3 response after TRH was measured. In addition a TRH test was performed 1–2 weeks after surgery in 11 patients.

The basal serum TSH did not differ from euthyroid control values in any of the groups and no late effect of hypophysectomy was observed. Subnormal peak TSH values were seen in 10 out of 37 euthyroid patients, whereas 9 out of 11 hypothyroid patients responded normally. Hypophysectomy caused an immediate but transient decrease in peak TSH in patients with a chromophobe adenoma only. The rise in serum T3 after TRH was significantly lower in hypophysectomized patients than in controls. An increase in TSH was followed by a T3 response in all patients except in 4 out of 8 euthyroid acromegalics. In patients operated on for a chromophobe adenoma the T3 response was correlated with serum T4, whereas this was not the case in acromegalics.