bluuebunny/crossref_metadata_2025 huggingface dataset:
PRE-OVULATORY CHANGES IN RAT FOLLICULAR CYCLIC AMP AND SENSITIVITY TO GONADOTROPHINS
Authors: Nilsson L. , Hillensjö T. , Ekholm C.
Published: December 2008

Stimulation of ovarian follicles by high concentrations of gonadotrophins has been reported to induce a refractory state in the follicles to further stimulation by the same agent. The present study was undertaken to determine whether a physiological gonadotrophic stimulus would induce a similar desensitization.

The levels of cyclic AMP (cAMP) were measured in rat pre-ovulatory follicles before and after the estimated period of gonadotrophin release. The PMSG injected pre-pubertal rat was used as a model of spontaneous ovulation as previously described. Follicles were explanted before and after the period of gonadotrophin release on the day before ovulation (day 30 in the present model) and cAMP was measured either directly or after 1–2 h of incubation. The follicles explanted in the evening of day 30 showed higher levels of cAMP than those isolated in the same morning irrespective of their being incubated or not. Follicular lactic acid production and progesterone synthesis as measured in the incubation medium showed the same pattern. The increase in all three parameters in "evening follicles" could be prevented by giving the animals pentobarbitone before the estimated gonadotrophin release. When the follicles were extirpated in the evening of day 30 and incubated in the presence of LH or FSH, significantly higher concentrations of the two hormones were needed to elicit a further increase in cAMP as compared to follicles isolated in the morning of the same day or from rats treated with pentobarbitone.

It is concluded that the pre-ovulatory surge of gonadotrophins induces a desensitization of the cAMP system of rat ovarian follicles toward further action by LH or FSH. This refractory state, however, is not complete but relative under physiological conditions.

In the rat, the duration of this phenomenon seems to coincide with the slight but significant elevation of follicular cAMP and to last from a few hours after the gonadotrophin surge up to ovulation. Possible mechanisms of this effect as well as its purpose are discussed.
FAILURE OF LUTEINIZING HORMONE - RELEASING HORMONE AND INSULIN TO FURTHER AUGMENT THYROTROPHIN RELEASE IN PRIMARY HYPOTHYROIDISM
Authors: Harrower A. D. B. , Yap P. L. , Cameron E. H. D. , Lidgard G. P.
Published: December 2008

The effect of luteinizing hormone - releasing hormone (LH-RH) and insulin-induced hypoglycaemia on the release of thyrotrophin (TSH) was studied in five patients with primary hypothyroidism. All five patients had elevated TSH levels with an exaggerated rise in response to thyrotrophin-releasing hormone (TRH). No rise over control values was found after LH-RH or insulin indicating that despite the augmentation of TSH release in primary hypothyroidism there is no alteration of the specificity of the thyrotroph response.
THE EFFECT OF A PLACENTAL MAMMOTROPHIN AND CORTISOL ON THE ULTRASTRUCTURE OF RAT MAMMARY GLAND IN ORGAN CULTURE
Authors: Njio K. D. , Peters J. M.
Published: December 2008

Mammary gland explants obtained from 13 days pregnant rats were cultured for 3, 6 and 9 days in the presence of serum of either virgin rats or 13 days pregnant rats. Insulin was added alone or in combination with cortisol. The way these different forms of treatment affected the ultrastructure was studied.

With virgin rat serum plus insulin alone the mammary gland regressed to a lower state of development comparable to that of the virgin rat in vivo. When virgin rat serum was replaced by 13 days pregnant rat serum - which contains rat chorionic mammotrophin - the initial development was maintained, but synthesis of secretory products ceased.

When cortisol was added to the virgin rat serum plus insulin, cortisol maintained the differentiated state originally present. Even some secretory activity was induced, but at a minimal level. With cortisol added to the pregnant rat serum plus insulin, the explants were stimulated to synthetize and extrude secretion products.
INFLUENCE OF PSORALEN ON MELATONIN FORMATION IN RAT PINEAL GLAND IN ORGAN CULTURE
Authors: Bäckström Maria , Wetterberg Lennart
Published: December 2008

8-Methoxypsoralen (10−4 m) added to the medium of rat pineal glands in organ culture induces a five-fold increase of 14C-labelled N-acetylserotonin and melatonin formation when serotonin is used as 14C-labelled precursor. Addition of d-amphetamine (10−5 m) to pineal glands also results in an increase of N-acetylserotonin and melatonin formation. This increase is enhanced by the addition of 8-methoxypsoralen (10−5 m). In pineal glands pre-incubated for 24 h 8-methoxypsoralen (10−4 m) caused an increased production of N-acetylserotonin and melatonin. This indicates that the effect of 8-methoxypsoralen is mediated through a post-synaptic event and not by release of noradrenaline or blocked re-uptake of amines to nerve terminals in the pineal gland. Further studies of the clinical significance of the effect of psoralen on pineal gland metabolism seems warranted.
THE EFFECT OF 2-BROMO-α-ERGOCRYPTINE AND 2-CHLORO-α-METHYLERGOLINE-8β-ACETONITRILE (LERGOTRILE MESYLATE) ON THE PROLACTIN SECRETION OF THE EWE
Authors: Hooley R. D. , Fell L. R. , Findlay J. K.
Published: December 2008

The effects of two ergot alkaloids, 2-bromo-α-ergocryptine methane-sulphonate (CB154, Sandoz) and lergotrile mesylate (LM, E. Lilly & Co.), on the basal secretion of prolactin and on the prolactin response to TRH or the milking stimulus was investigated in the sheep. Both CB154 (c. 0.5 mg/kg) and LM (c. 0.75 mg/kg) markedly reduced basal levels of prolactin and inhibited the TRH-induced prolactin release in ewes in the mid-luteal phase of the oestrous cycle. Both compounds also suppressed basal levels of prolactin in lactating ewes and inhibited the prolactin response to the milking stimulus in lactating ewes.
VASOPRESSIN TEST: DIAGNOSTIC INACCURACY IN EVALUATION OF HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS
Authors: Leisti Seppo , Perheentupa Jaakko
Published: December 2008

An im vasopressin test was given to 141 children and adolescents, 52 with normal HPA axis and 89 with evident or suspected defect of the axis, and repeated in 36 cases, to establish criteria of a normal response, and to examine the accuracy and precision of the responses. Comparisons were made with the responses to the 2-h ACTH, insulin and 3-h metyrapone test.

The distributions of plasma cortisol levels and increments were positively skew, and a log transformation was made for appropriate statistical analysis. Maximal plasma cortisol level was positively and maximal increment negatively correlated with the basal level. In precision, the maximal level was superior to the maximal increment. Hence, a normal result was best defined by an area around the regression of maximal level on basal level in the normal series. The best single index of the response was the maximal level. A useful new method was introduced for quantitative comparison of plasma cortisol responses to different tests.

The vasopressin test result was frequently normal in patients who, according to repeated insulin tests were ACTH-deficient. Furthermore, the 10 patients with organic expansive hypothalamic lesions had a mean vasopressin response, that was greater relative to the insulin response than that of the reference series. However, 3 of 21 patients with organic non-expansive hypothalamic disease gave a subnormal vasopressin response but a normal insulin response. Moreover, in isolated GH deficiency and after prednisone medication the mean vasopressin response was lower relative to the insulin response than in the reference series. Thus, this test is not reliable in screening for, or in anatomical diagnoses of ACTH deficiency.
EFFECTS OF SEX STEROIDS ON GROWTH HORMONE PRODUCTION IN CULTURED RAT PITUITARY CELLS
Authors: Haug E. , Gautvik K. M.
Published: December 2008

Monolayer cultures of rat pituitary tumour cells (GH3) were used to study the effects of different sex steroids on growth hormone (GH) production expressed as the amount of extracellular hormone which accumulated during 24 h. The hormone was measured with a sensitive and specific radioimmunoassay.

Oestradiol-17β (10−12 mol/l—10−6 mol/l) caused a dose-dependent decrease in GH production with the maximum effect (30 % of controls) at 10−10 mol/l. After the cessation of treatment with oestradiol-17β (10−8 mol/l for 7 days), control levels of GH were obtained within 11 days, after a transient augmentation of production. Progesterone (10−11–10−6 mol/l) caused a dose-dependent stimulation of GH production, and the maximum effect (160 % of controls) was observed at 10−6 mol/l. Testosterone (10−6 mol/l) decreased the production of GH to 70 % of control values, whereas 5α-dihydrotestosterone (DHT) had no effect. Cell growth was not affected by any of the sex steroids. Corticosterone (10−6 mol/l) increased GH production to about 400 % of control values, and this effect was inhibited by oestradiol-17β (10−6 mol/l). The hypothalamic peptides, thyrotrophin releasing hormone (TRH) and somatostatin, that both depressed GH production did not significantly inhibit the stimulatory effect of corticosterone. When used in combination, the effects of oestradiol-17β (10−6 mol/l) and TRH (3 × 10−7 mol/l) were additive which was not the case for the combination oestradiol-17β (10−6 mol/l) and testosterone (10−6 mol/l).

These results suggest different mechanisms of action of peptide and steroid hormones on GH production in the GH3 cells. If the properties of the GH3 cells reflect those of normal somatotrophs the sex steroids may alter GH production at the pituitary level, an influence that may be further modulated by corticoids, TRH and somatostatin.
RADIOIMMUNOASSAY OF THYROTROPHIN-RELEASING HORMONE (TRH) IN NORMAL SUBJECTS, IN ABNORMAL THYROID STATES AND UNDER CATECHOLAMINERGIC INFLUENCES
Authors: Lombardi G. , Panza N. , Cei S. , Cosimato F. , Minozzi M.
Published: December 2008

Plasma TRH was determined by radioimmunoassay in normal and abnormal thyroid state. In euthyroid adult subjects, the plasma TRH level were 31.9 ± 11 pg/ml (mean ± sd). No significant differences were observed with regard to sex, pregnancy or age, except for the acute increase in newborn infants. The plasma TRH levels evaluated in abnormal thyroid states were found significantly (P < 0.001) increased in hyperthyroidism (49.1 ± 14 pg/ml) and decreased in hypothyroidism (22.1 ± 6 pg/ml). Nor were any significant differences observed in simple goitre, pituitary adenoma and empty sella. Lastly, plasma TRH and TSH levels were also evaluated after acute administration of L-dopa, 2-Br-α-ergocriptine and chlorpromazine in normal and hypothyroid subjects. Contemporaneous modifications of plasma TRH and TSH levels (decreased after L-dopa and 2-Br-α-ergocriptine, increased after chlorpromazine) were observed in hypothyroidism.

The results indicate that plasma TSH modifications at birth as well as under catecholaminergic influences are at least partially mediated by variations of TRH secretion. Moreover, the inverse plasma TRH and TSH modifications in abnormal thyroid states agree with different feedback effects at the hypothalamic (positive) and pituitary (negative) level. It is possible that the significance of the positive feedback at the hypothalamic levels can be interpreted when taking into account the extra-pituitary effects of TRH.
OPPOSITE VARIATIONS IN SERUM T3 AND REVERSE T3 DURING PROPYLTHIOURACIL TREATMENT OF THYROTOXICOSIS
Authors: Laurberg Peter , Weeke Jørgen
Published: December 2008

Blood samples for determination of serum total and free reverse triiodothyronine (rT3), triiodothyronine (T3) and thyroxine (T4) were obtained daily in 6 previously untreated thyrotoxic patients during periods of propylthiourazil (PTU) (600 mg per day) or methimazol (MMI) (45 mg per day) administration.

PTU induced about 60 per cent increase in both total and free serum rT3. This was accompanied by a rapid decrease in serum T3 and a more gradual decline in serum T4. MMI administration to untreated patients was followed by a gradual parallel decrease in rT3, T3 and T4. Turn from PTU to MMI produced a rapid decrease in serum rT3 and increase in serum T3 in all 6 patients. The relative variations in the free and total concentrations of iodothyronines were practically identical.

The increase in serum rT3 after PTU is most likely explained either by enhanced deiodination of T4 to rT3 or by an inhibitory effect of PTU on rT3 degradation.
THE TEST OF OVERLOADING OF L-DIIODOTYROSINE (DIT) IN THE SCREENING OF IODOTYROSINE DEHALOGENASE DEFICIENCY
Authors: Codaccioni J. L. , Rinaldi J. P. , Bismuth J.
Published: December 2008

The hereditary nature of goitrous hypothyroidism due to the iodotyrosine dehalogenase deficiency (IDD) has been suspected. In order to demonstrate a partial deficiency in the relatives and parents of the patients we studied, using urinary elimination, the peripheral deiodination of labelled L-diiodotyrosine (DIT). The usual procedure consists of a standard test which was performed by iv injection of a tracer dose of radioactive DIT. In order to increase the sensitivity of the method we used a test of overloading, carried out by iv administration of 20 to 25 mg of highly purified [127I]L-DIT labelled with 50 μCi of 125I in adults and a lower dose in children. After injection the quantity of non-deiodinated DIT was measured in urinary samples at intervals of 0 to 2, 2 to 6 and 6 to 24 h. In 15 normal subjects the urinary elimination of DIT in 6 h varied from 1.9 to 23.9% of the injected dose. In 8 goitrous hypothyroid patients, 52 to 79.9 % was eliminated, most of the excretion occurring during the first 2 h. In 22 relatives of the patients it was 6.9 to 43 % of the dose, and in one of the patient's relatives who was clinically normal it was 70.9 %.

A statistically study showed that the most significant characteristic was the percentage of DIT excreted during the first 2 h. Elimination in the normal group was 11.4% (sd 5.8) while that of the parents and relatives of goitrous hypothyroid patients was 20.4 % (sd 12.5). Thus the 2 groups are statistically different but with a poor P-value (P < 0.05). Discriminant analysis permitted classification of each relative with respect to the control group: among 23 parents and relatives, 15 differed from the controls and were suspected of representing a partial IDD. The latter can be considered as heterozygotes, and according to the results of the proposed DIT overloading test the transmission of congenital IDD is determined as an autosomal recessive trait. However, in one family, the hypothesis of the variable expressivity of a genetic dominant trait must be considered.
STEROID METABOLISM IN THE PERFUSED HUMAN PLACENTA
Authors: Wolf Alfred S. , Musch Klaus A. , Speidel Werner , Strecker Jürgen R. , Lauritzen Christian
Published: December 2008

A new model for the perfusion of human term-placentas has been developed for studies on the placental biogenesis of C-18 and C-19 steroids. For viability criteria, the glucose- and oxygen-consumption, regional perfusion control by dye-infusions or scanning after injection of 99Tc-labelled macroparticles, and the histological qualification were chosen. The recycled perfusate was investigated for the steroids oestrone (Oe1), oestradiol-17β (Oe2), oestriol (Oe3), 4-androstene-3,17-dione (A), testosterone (T), and human placental lactogen (HPL) by radioimmunoassay in controls and perfusions with the foetal steroid precursor dehydroepiandrosterone sulphate (DHA-S). In control perfusions, steroid hormones were found in constant ratios (Oe1:Oe2:Oe3:T:A = 30:1.5:100:0.35:1). Following the administration of 10 mg DHA-S for testing the metabolic capacity of the organ, high concentrations of Oe1 (90–720 ng/ml = 250–3970 % as compared to 100% pre-injection values) were found, shortly preceded by a rapid increase of A (66–1000 ng/ml = 100–16 000 %). A typical surge of T (5.3–147 ng/ml = 265–4640 %) preceded the normally slower increment of Oe2 (22–220 ng/ml = 1570–4330 %). The concentrations of Oe3 and HPL remained nearly unchanged. From different steroid patterns after DHA-S-load, two distinct responses of term-placentas could be differentiated: Group I (n=12) showed high concentrations of Oe1 (3200 ± 940 %), a small increase of T (1020 ± 500%), as well as low and delayed values of Oe2 (1660 ± 450%). In Group II (n = 5), values were high for T (3160 ± 1020%) and Oe2 (3300 ± 1110%), whereas Oe1 was found in a lower range (508 ± 302%).

In contrast to in vivo findings in maternal venous blood after DHS-S injection to the mother, oestrone was found in perfusions as the main oestrogen fraction from DHA-S. Thus, the analysis of such metabolic differences might be of help in the interpretation of complex results from the DHA-S-loading test.
INDUCTION OF PREMATURE PARTURITION IN SHEEP: ADRENOCORTICOTROPHIN AND CORTICOSTEROID CHANGES DURING INFUSION OF SYNACTHEN INTO THE FOETUS
Authors: Jones C. T. , Johnson P. , Kendall J. Z. , Ritchie J. W. K. , Thorburn G. D.
Published: December 2008

Synacthen (10 μg/h) infused into foetal sheep at about day 125 of gestation caused premature delivery within 4 days. During the first 24 h of the infusion the secretion of adrenocorticotrophin was depressed and the assayable hormone concentration was within 500–1000 pg/ml. Subsequently, large fluctuations occurred in the adrenocorticotrophin concentration in the pasma of foetal sheep which were consistent with the stimulation of adrenocorticotrophin secretion. No transfer of Synacthen to non-infused twin foetuses was observed. The plasma corticosteroid concentration in the infused foetus also showed a small rise during the first 24 h of the infusion followed by large fluctuations in concentrations that coincided with the changes in adrenocorticotrophin. No consistent changes in the plasma corticosteroid concentration in the non-infused twin foetus were observed. These results are discussed in relation to the hormone changes occurring during normal delivery.
PROLACTIN-LOWERING EFFECT OF LOW DOSES OF LISURIDE IN MAN
Authors: Horowski R. , Wendt H. , Gräf K.-J.
Published: December 2008

Lisuride, a new semisynthetic ergot derivative, effectively decreased the TRH-induced hyperprolactinaemia in healthy female volunteers at a dose of 300 μg given orally. Basal prolactin levels were suppressed after a single dose of 100 and 200 μg lisuride. This effect was still present 6 h after administration. Two hundred μg lisuride also decreased the high serum prolactin levels produced by im injection of 50 mg sulpiride, and conversely, sulpiride injection abolished the prolactin lowering effect of lisuride. These results demonstrate that in man too lisuride is a very potent prolactin-lowering agent. In addition, the data support the hypothesis of a predominant role of dopaminergic mechanisms in the regulation of prolactin secretion.
SHORT-TERM REGULATION OF LH AND FSH SECRETION IN CYCLIC WOMEN
Authors: Römmler A.
Published: December 2008

The effects of two iv 25 μg LH-RH injections (180 tests) at different intervals (30 min to 24 h) on radioimmunoassayable serum LH and FSH levels were investigated in 30 women in the midfollicular or midluteal phase of the menstrual cycle.

The pituitary LH and FSH response to the second LH-RH injection at time-intervals of 30 and 360 min was significantly lower than the response elicited after the first injection. The second response was significantly higher at 60 to 180 min intervals. The maximum increment occurred at 120 min. No significant differences between the two pituitary responses to LH-RH were found at intervals of 240 min and 24 h.

A theory with regard to intracellular processes of hormone synthesis and degradation is proposed to explain these time-dependent differences in the pituitary LH and FSH response.
IMPORTANCE OF INSULIN SECRETION BASED ON THE RATE OF CHANGE IN BLOOD GLUCOSE CONCENTRATION IN GLUCOSE TOLERANCE, ASSESSED BY THE ARTIFICIAL BETA CELL
Authors: Kawamori Ryuzo , Shichiri Motoaki , Goriya Yoshikazu , Yamasaki Yoshimitsu , Shigeta Yukio , Abe Hiroshi
Published: December 2008

The dynamic property of glucose-induced insulin secretion was simulated with the aid of a control theory, and the relationship between the stepwise input of glucose concentration and the biphasic response of insulin as an output was expressed in the transfer function of proportional plus derivative action to glucose concentration. By utilizing this model, the following computer algorithm for the artificial beta cell was made; rate of insulin infusion = Kp BG + Kd ΔBG+ Kc, where BG was the abbreviation for glucose concentration, ΔBG was the rate of change in BG, Kp and Kd were the coefficient for the proportional and derivative action, respectively, and Kc the constant for basal insulin secretion.

Microcomputer, insulin pump and digital printer were packed in small case, which was connected with glucose analyzer.

Experiments were carried out in the depancreatized dogs to validate the importance of infused insulin based on derivative action to glucose concentration in glucose regulation. Kd/Kp ratio was changed when insulin was infused following iv glucose bolus injection. The results revealed that when the derivative action was added to the proportional action properly in insulin infusion regulatory system, insulin requirement was the smallest and glucose regulation was the best.

The characteristics of the system recognized in clinical application were 1) rate of insulin infusion was small enough to keep the plasma concentration of insulin at a physiological level, then insulin requirements were reduced to around a half of those given subcutaneously, 2) glucose or glucagon to restore hypoglycaemia was not essential.
ROLE OF CYCLIC AMP IN OOCYTE MATURATION AND GLYCOLYSIS IN THE PRE-OVULATORY RAT FOLLICLE
Authors: Hillensjö Torbjörn , Ekholm Carl , Ahrén Kurt
Published: December 2008

This study was undertaken in order to analyse the role of cyclic AMP (cAMP) in the stimulatory action of LH on the resumption of oocyte meiosis (oocyte maturation) and follicular glycolysis. Follicular development was induced in immature rats by a single injection of pregnant mares' serum gonadotrophin. Pr-ovulatry follices were extirpated on the day before ovulation and incubated in a chemically defined medium for 4–10 h. The follicle-enclosed oocytes remained in the dictyate stage when incubated in hormone-free medium but in the presence of LH oocyte maturation was induced. When cAMP or butyryl derivatives of cAMP were added to the incubation medium no effect on the oocyte was seen. However, these nucleotides prevented the stimulatory action of LH on the oocytes. The phosphodiesterase inhibitors theophylline and IBMX had similar effects as cAMP on oocyte maturation, causing a reversible blockage of the LH effect. When 8-Br-cAMP and the phosphodiesterase inhibitor ICI 63.197 were tested it was found that both had inherent stimulatory effects on oocyte maturation at certain concentrations. Pre-incubation of the follicles in a high concentration of dibutyryl cAMP followed by transfer to plain medium resulted in oocyte maturation.

Follicular lactate production was stimulated by all cyclic nucleotide derivatives tested, except cAMP, and by IBMX and ICI 63.197. There was no reduction by these agents of the stimulatory effect of LH on lactate production.

A model to explain the role of cAMP in oocyte maturation is presented.
FERTILE EUNUCH SYNDROME VERSUS CLASSIC HYPOGONADOTROPHIC HYPOGONADISM
Authors: Smals A. G. H. , Kloppenborg P. W. C. , van Haelst U. J. G. , Lequin R. , Benraad T. J.
Published: December 2008

The functioning of the hypothalamo-pituitary-target organs axis was assessed in 3 patients with 'fertile eunuch' syndrome (FE) and 6 patients with 'classic' hypogonadotrophic hypogonadism (HH) with or without hyposmia. Both groups of patients did not differ from each other with regard to basal serum prolactin levels, pituitary growth hormone and thyrotrophin reserve and the thyroid or adrenal gland function. Both groups differed, however, with respect to the hypothalamo-pituitary-gonadal function: 1. the pituitary LH response to exogenous LH-RH was (low)-normal in FE and blunted in HH; 2. the basal FSH levels were normal in FE and undetectable in HH; 3. the basal LH levels were normal in FE and 3/6 patients with HH and low in the remaining three; 4. the basal and HCG stimulated plasma testosterone concentrations were significantly higher in FE than HH. The data suggest that FE represents a less severe form of LH-RH deficiency, rather than a distinct disorder.
SUPRAHYPOPHYSEAL DYSFUNCTION IN A PATIENT WITH ASEXUAL ATELEIOSIS
Authors: Medina Martha , Parra Adalberto , Scaglia Hugo E. , Nieto Laura , Pérez-Palacios Gregorio
Published: December 2008

The neuroendocrine function of a 19 years old female dwarf with primary amenorrhoea and lack of sexual development (asexual ateleiosis) was studied. Undetectable fasting plasma levels of growth hormone (GH) and a lack of response to three different provocative stimuli was observed. Oestrogen administratin did not modify the GH response. Thyroid and adrenal function were within normal limits. Undetectable plasma levels of immunoreactive oestradiol and lack of oestrogenic activity in vaginal smears indicated absence of ovarian function. Low levels of circulating gonadotrophins with a significant rise after synthetic LH-RH administration was demonstrated, while clomiphene citrate failed to induce ovulation. Following 6 months of continuous GH administration a significant increase in the growth rate was evident, whereas no pubertal development was observed. These data are interpreted as demonstrating the suprahypophyseal origin of the sexual infantilism in a patient with inappropriate GH secretion. It is suggested that a combined deficiency of LH-RH and GH-RH may account for the aetiology of this disorder.
PITUITARY STIMULATION TEST IN AMENORRHOEIC PATIENTS WITH NORMAL OR LOW SERUM OESTRADIOL
Authors: Kletzky Oscar A. , Mishell Daniel R. , Davajan Val , Nicoloff John , Mims Robert , Nakamura Robert M.
Published: December 2008

A group of 15 patients with secondary amenorrhoea were studied. In 8 of these patients (hypothalamic-pituitary dysfunction, HPD) the baseline plasma Oe2 concentration (47.7 ± 6.0 pg ml) was similar to the early follicular phase levels of the 9 control subjects (48.8 ± 3.3 pg/ml). The remaining 7 patients (hypothalamic-pituitary failure, HPF) had significantly lower plasma Oe2 values (19.8 ± 2.6 pg/ml). Plasma LH and FSH levels were similar in the two groups of patients as well as the controls. All patients and control subjects were sequentially stimulated with insulin induced hypoglycaemia, GnRH-TRH and then GnRH alone. Although abnormal GH and PRL responses to hypoglycaemia and blunted PRL responses to TRH were obtained in the two groups of patients the results could not be correlated with plasma Oe2 baseline values. In both groups of patients, cortisol and TSH responses were comparable to the control subjects. Following the administration of GnRH the maximum LH response in patients of the HPF group was significantly lower (P < 0.025) than the LH response in patients of the HPD group. No statistically significant difference was found in the FSH response between the two groups.

In conclusion, most of the patients with secondary amenorrhoea due to HPD have been shown to have most probably a hypothalamic derangement. Patients with HPF may have either a more profound hypothalamic involvement or an intrinsic pituitary alteration.
ABNORMAL RESPONSE OF LUTEINIZING HORMONE, FOLLICLE STIMULATING HORMONE AND TESTOSTERONE TO LUTEINIZING HORMONE-RELEASING HORMONE IN CHRONIC RENAL FAILURE
Authors: Hasegawa Koichi , Matsushita Yoshiki , Hirai Kenzo , Otomo Seima , Okamoto Teruo , Morii Hirotoshi , Wada Masahisa
Published: December 2008

Serum levels of LH, FSH, testosterone and oestradiol were measured by radioimmunoassay in 10 healthy subjects and 7 undialysed and 15 dialysed patients with chronic renal failure. The basal level of serum LH was significantly higher in patients with chronic renal failure than in healthy subjects. The basal level of serum FSH in male subjects was significantly higher in dialysed patients with chronic renal failure than in healthy subjects. Regarding testosterone secretion in male subjects and oestradiol secretion in female subjects, it was shown that the basal level of serum testosterone was significantly lower in patients with chronic renal failure than in healthy subjects, and that serum oestradiol levels were within the normal range in most of the patients with chronic renal failure. Serum levels of LH, FSH and testosterone were determined after iv injection of 100 μg of LH-RH in three groups of subjects. Responses of serum LH and FSH to LH-RH were exaggerated and prolonged in patients with chronic renal failure compared with healthy subjects. The peaks of serum LH and FSH were observed 30 min after LH-RH injection in healthy subjects while those in chronic renal failure appeared at 60 to 120 min. The levels of serum testosterone after LH-RH injection did not change within 120 min.

These findings may indicate that the pituitary gonadotrophin response to LH-RH is abnormal and that the turnover of LH, FSH and LH-RH is decreased in patients with chronic renal failure.
THE ACTIVITY OF AN LH-RH-DEGRADING ENZYME IN THE ANTERIOR PITUITARY DURING THE RAT OESTRUS CYCLE AND ITS ALTERATION BY INJECTIONS OF SEX HORMONES
Authors: Kuhl Herbert , Rosniatowski Christian , Taubert Hans-Dieter
Published: December 2008

The basal activity of an LH-RH-degrading enzyme system, L-cystine arylamidase, was determined in the pituitary gland of female rats at 4 h intervals throughout the 4-day oestrus cycle. The activity of the enzyme was found to be fluctuating during the four stages of the cycle in a circadian rhythm with the highest values occurring at night and the lowest values at noon. The maximal activity for the whole cycle was measured at 04.00 h on the day of metoestrus, and the minimal activity between 12.00 h and 16.00 h on the day of pro-oestrus.

The iv injection of various doses of oestradiol caused only a slight change in enzyme activity of the pituitary during oestrus, but considerable increases were observed during the other three stages. The stimulation of enzyme activity by progesterone was much more pronounced during dioestrus and pro-oestrus as compared with metoestrus and oestrus. Similarly the reaction to the injection with LH and prostaglandin E2, repectively, were not very pronounced during oestrus and metoestrus, whereas the enzyme activity rose by +50% and +100%, respectively, during dioestrus and pro-oestrus.

The LH-RH-degrading enzyme system in the pituitary seems to be involved in the control of the tonic LH release, and in the maintenance and regulation of the sensitivity of the gonadotrophs to alterations in LH-RH release from the median eminence.
SYSTOLIC TIME INTERVALS (STI) AS INDICATORS OF MYOCARDIAL THYROID HORMONE EFFECT
Authors: Chakravarty J. , Guansing A. R. , Chakravarty S. , Hughes C. V.
Published: December 2008

Systolic time intervals consisting of indices of electromechanical systole (QS2-I), left ventricular ejection time (LVET-I) and pre-ejection period (PEP-I) were calculated serially during therapy in 12 euthyroid, 9 hypothyroid and 9 hyperthyroid individuals. These parameters were analyzed sequentially together with the changes in serum thyroxine (T4), triiodothyronine (T3) and thyrotrophin (TSH) in order to determine the sensitivity of these non-invasive procedures in monitoring peripheral thyroid hormone effect. The results are expreseed in mean ± sem. QS2-I (506.3 ± 8.2 ms) and PEP-I (102.9 ± 4.2) were shortened (P < 0.02 and P < 0.001, respectively) in hyperthyroidism and prolonged (579.3 ± 7.3 and 169.6 ± 3.6 ms) in hypothyroidism (P < 0.01 and P < 0.001, respectively) compared to euthyroid controls (538.1 ± 8.8 and 130.3 ± 5.3 ms), while LVET-I did not change significantly in either condition. Simultaneous determinations of circulating T4, T3 and TSH showed changes appropriate to both hypo- and hyperthyroid states. In 2 patients with T3-thyrotoxicosis, PEP-I was decreased to an average of 103.1 ms, while in 2 patients with compensated hypothyroidism (normal T4 but elevated TSH) this was prolonged to 163.7 ms (average) compared to euthyroid controls. During treatment the hypothyroid group showed significant sequential correlation of TSH and PEP-I. In the hyperthyroid individuals, PEP-I correlated significantly with T4 and T3. PEP-I may be a useful, sensitive, quantitative biologic indicator of thyroid hormone effect on myocardial function.
DEVELOPMENT OF THE INSULIN SECRETORY DEFECT IN GENETICALLY DIABETIC (db/db) MOUSE
Authors: Berglund Ove , Frankel Barbara J. , Hellman Bo
Published: December 2008

Genetically diabetic mice (C57BL/KsJ-db/db) were used as a model to study the development of defects of insulin secretion in relation to common metabolic indicators (body weight, serum glucose and insulin, and islet insulin contant). Consistent with the idea of a protective effect of oestrogen on the pancreatic β-cell, the female diabetic mice survived longer than the males. In males, while serum insulin decreased in the later stages of the disease, serum glucose increased progressively with age. Perfusion of the diabetic pancreases revealed a rise and subsequent fall with age of the basal insulin released at 3 mm glucose. Despite previous reports of β-cell hyperplasia, progressive impairment of the insulin response to 20 mm glucose, or to 20 mm glucose and 1 mm 3-isobutyl-1-methylxanthine, was seen with increasing age in experiments with perfused pancreas or microdissected islets. Islet content of insulin also decreased progressively with age in the diabetic animals.
THE METABOLISM OF PROSTAGLANDIN E2 BY TISSUES FROM THE HUMAN UTERUS AND FOETO-PLACENTAL UNIT
Authors: Willman Eve A. , Collins W. P.
Published: December 2008

The biosynthesis and metabolism of prostaglandin E2 was studied in cell-free homogenates of tissues from the uterus and foeto-placental unit using specific in vitro methods.

The results show that the synthesis of prostaglandin E2 is greater in endometrial tissue from the secretory phase (53.07 ± 39.05; ng/100 mg wet tissue/h) than from the proliferative phase of the uterine cycle. Furthermore, endometrial tissue forms more of this compound than myometrium (P < 0.005). During early pregnancy, synthesis is decreased (25.10 ± 16.62); at term, myometrium produces more prostaglandin E2 than decidua. During labour, however, decidual tissue accumulates more of this compound (52.73 ± 18.04) than either myometrium (34.71 ± 13.19) or cord (28.63 ± 11.71).

The catabolic enzymes are most active in the placenta and chorion, followed by the cord, myometrium, decidua and amnion, but the differences have only a slight effect on the amounts of prostaglandin E2 which remain at the end of the incubation. The results suggest a high turnover of prostaglandin E2 in the decidua, myometrium and cord.
PYRIDOXINE TREATMENT OF GALACTORRHOEA-AMENORRHOEA SYNDROMES
Authors: Lehtovirta P. , Ranta T. , Seppälä M.
Published: December 2008

The effect of pyridoxine (B6) on galactorrhoea, amenorrhoea, and the galactorrhoea-amenorrhoea syndrome was studied in 22 patients. No consistent change in serum prolactin concentration and no resumption of ovulation were seen during 3 months B6 therapy. Inappropriate lactation ceased in 3 of 10 patients with galactorrhoea alone, and menses were restored in 2 of 9 patients with the galactorrhoea-amenorrhoea syndrome while on B6 therapy. Our results suggest that B6 is not generally effective in the treatment of galactorrhoea-amenorrhoea syndromes.
LONG-TERM TREATMENT OF ACROMEGALY WITH BROMOCRIPTINE
Authors: Eskildsen Peter Claes , Svendsen Per Aaby , Vang Lisbeth , Nerup Jørn
Published: December 2008

Treatment with bromocriptine, 30–55 mg daily, in 13 acromegalics for 1–15 months, resulted in a 60 % decrease in growth hormone secretion, as judged from the excretion of growth hormone in 24-h urine. Normal excretion was obtained in 10 patients, while 1 patient showed no response. The plasma growth hormone response to O-GTT was improved, but not normalized, in 4 of 7 patients treated for more than 6 months, and marked glucosuria disappeared in two diabetics. While the secretion of TSH, LH and FSH was unchanged, the prolactin secretion was inhibited. The urine excretion of free cortisol showed a 30 % decrease, possibly due to a direct effect of bromocriptine on the ACTH-secretion. Hypercalcaemia was never seen, but the initial hypercalcuria showed a modest decrease without measurable changes in the creatinine clearance. The subjective relief during long-term treatment was marked in 10 of 11 patients and the dominating symptoms disappeared in 40–67 %, whereas heal-pad thickness, enlarged sellae, and visual fields remained unchanged. No serious side effects were observed. Treatment with bromocriptine seems effective and should be considered as a remedy amongst others, in suitable cases of acromegaly.
PROLACTIN SECRETION AND SYNTHESIS IN SHORT- AND LONG-TERM ORGAN CULTURE OF PITUITARY TUMOURS FROM ACROMEGALIC PATIENTS
Authors: Peillon F. , Cesselin F. , Garnier P. E. , Brandi A. M. , Donnadieu M. , L'Hermite M. , Dubois M. P.
Published: December 2008

To evaluate the in vitro PRL secretion and synthesis by pituitary tumours from acromegalic patients, six somatotrophic and two somatomammotrophic adenomas were collected after surgery and divided into fragments 1 mm3 in size. Fragments were cultured in short-term (1–2–3–4 h) and in long-term organ culture (7 and 14 days). Media were collected for GH and PRL radioimmunoassay and fragments studied by electron microscopy. In two experiments, fragments from a somatotrophic adenoma and from a somatomammotrophic adenoma were cultured for 1 to 4 h and 9 to 16 days with [3H]leucine. In addition the effect of somatostatin (2.5 nmole/ml) upon PRL secretion was studied in short-term incubation. In long-term organ culture PRL concentrations increased in 8 out of 16 media samples collected from the five tumours and one normal pituitary cultured for 14 days, while GH concentrations decreased during the same time in all the experiments. The [3H]PRL/[3H] proteins ratios were 9.7 % on the 9th day of culture and 20.8 % on the 16th day while for GH, the ratios were respectively 40 and 34.7 %. Ultrastructural studies showed, besides GH cells, the presence of PRL secreting cells in the different tumours, after 7 or 14 days of culture. In short-term incubation, PRL concentrations in media increased in most of the samples collected from the three tumours incubated for 1 to 4 h and the [3H]PRL/[3H]proteins ratio was 10.6 % after 1 h and 21 % after 2 h of incubation. A decrease of PRL content (< 50 %) was observed in two of the three tumours incubated with somatostatin.

These data indicate that 1) somatotrophic adenomas, as well as somatomammotrophic ones, are able to secrete and synthesize PRL in vitro, 2) PRL synthesis from these adenomas increases during culture, as from normal pituitary, presumably because of the release of PRL-secreting cells from the PRL inhibitory hypothalamic control (PIF), 3) somatostatin may reduce PRL release in vitro from somatotrophic adenomas as reported in some cases in vivo.
VASOACTIVE INTESTINAL PEPTIDE (VIP): TISSUE DISTRIBUTION IN THE RAT AS MEASURED BY RADIOIMMUNOASSAY AND BY RADIORECEPTORASSAY
Authors: Besson J. , Laburthe M. , Bataille D. , Dupont C. , Rosselin G.
Published: December 2008

This work was undertaken to study the distribution of VIP in the digestive tract. VIP was measured both by radioimmunoassay and by radioreceptorassay in order to determine whether immunoreactive VIP is related to a biologically active component.

The effect of digestive extracts in inhibiting the binding of porcine [125I]VIP to the antibody (RIA) and to the rat liver plasma membranes (RRA) paralleled that of porcine VIP used as the standard. VIP was found throughout the digestive tract with especially high concentrations between the duodenum (1676 ± 186 ng/g) and the colon (1214 ± 214 ng/g); the maximal quantity occurred in the jejuno-ileum (11 698 ± 687 ng/g). Less than 1 % of VIP was found in the epithelium whereas almost all VIP (> 99%) was localized in the mucosal muscular tissue of the jejunoileum. VIP concentration in the pancreas was 180 ± 26 ng/g of tissue. The VIP contents of the digestive tract were similar when measured either by radioimmunoassay or by radioreceptorassay. Immunoreactive VIP was found in the brain (155 ± 7 ng/g of tissue) and brain extracts competitively inhibited the binding of [125I]VIP (purified from gut) to liver plasma membranes.

These results show that: 1) VIP from the overall gastrointestinal tract is a biological active molecule: 2) VIP from brain binds to receptors for intestinal VIP in liver.
ADRENAL HYPERTROPHY PRODUCED BY 17α-ESTERIFIED GLUCOCORTICOIDS IN RAT FOETUS
Authors: Hasegawa Y. , Okamoto A. , Sakaguchi I.
Published: December 2008

Glucocorticoids were injected sc into rat foetuses through the uterine wall on day 19 of intrauterine development; two days later the foetuses were removed and their adrenal glands were weighed. Some betamethasone derivatives produced marked adrenal hypertrophy in the foetuses. Structural characteristics of the effective compounds were 17α-esterification and 16β-methylation. 9α-Halogenation and 21-esterification of glucocorticoids were not essential for producing the hypertrophy. Propionic acid at the C-17 position was more effective than valeric and acetic acids in producing the hypertrophy. The effect of betamethasone 17, 21-dipropionate was dose-responsive and prevented by simultaneous administration of betamethasone 21-disodium phosphate. Results obtained with decapitated or encephalectomized foetuses suggested that the hypertrophy produced was not due to a direct action of the glucocorticoids on the adrenal gland, but mediated by the hypothalamo-pituitary system.
EFFECT OF POLYAMINES AND THEIR OXIDIZED DERIVATIVES ON THE METABOLISM OF RAT EPIDIDYMAL SPERMATOZOA
Authors: Pulkkinen P. , Piik K. , Koso P. , Jänne J.
Published: December 2008

Spermine and spermidine, occurring at relative high concentrations in the secretions of male sexual glands of various mammals, greatly stimulated the fructolysis in rat epididymal spermatozoa. Calcium likewise had a stimulatory effect on fructolysis producing together with spermine a synergistic enhancement of spermatozoa sugar utilization. While enhancing fructolysis spermine and calcium were practically without any effect on the production of 14CO2 from [2-14C]lactate. Spermatozoal fructose utilization was also markedly increased upon addition of exogenous ATP, spermine producing an additional stimulation with the latter nucleotide.

In addition to spermine and spermidine, the diamines putrescine, 1,3-diaminopropane, cadaverine and histamine also significantly enhanced the formation of radioactive CO2 and lactate from uniformly labelled fructose.

The stimulation of lactate formation by spermine was lost in cell free extracts of spermatozoa. This and the fact that spermine (especially in the presence of ATP) was found to stimulate the uptake of fructose by the epididymal sperm cells suggests that the polyamines interact with cell membranes facilitating sugar uptake.

Oxidized spermine [N,N′-bis(3-propionaldehyde)-1,4-diaminobutane], a compound arising from the action of ruminant plasma amine oxidase, powerfully inhibited both the fructolysis and glycolysis in rat epididymal spermatozoa.
HISTAMINE STIMULATES PROLACTIN RELEASE IN NORMAL MEN
Authors: Pontiroli Antonio E. , Pozza Guido
Published: December 2008

Histamine stimulates prolactin (PRL) and growth hormone (GH) release in the experimental animal. In order to evaluate the possible effect of histamine on these hormones in man, in our study, 9 normal volunteers underwent an intravenous histamine infusion (200 μg in 15 min). Five of them also underwent an intravenous histidine infusion (200 μg). Histamine induced a significant PRL release in 7 subjects, the maximum level reached being 36.2 ± 12.09 ng/ml, while GH levels were not affected. Histidine was ineffective on both PRL and GH levels. It is known that histamine, administered peripherally, does not cross the blood brain barrier. This fact suggests that, in man, histamine stimulates PRL release by acting directly on the pituitary. In addition, since stressful situations may elicit both PRL and GH release, the fact that the latter was not affected by histamine, suggests that a mere stress-effect is not responsible for the PRL release observed in our subjects.
THYROXINE: STUDIES CONCERNING ITS INTRINSIC PHYSIOLOGICAL ACTIVITY
Authors: du Breuil Anne , Galton Valerie Anne
Published: December 2008

The importance of the monodeiodination of T4 to T3 in the physiological action of T4 was explored by assessing the role of T4 in maintaining propylthiouracil (PTU)-treated rats during exposure to 4°C. (PTU inhibits both thyroid hormone biosynthesis and T4 to T3 conversion in peripheral tissues.) Firstly, the effects of cold exposure on the metabolism of T4 in control and PTU-treated rats equilibrated with [125I]T4 (2 μg/100 g b. w./day) were determined. PTU was administered in the food (2 mg/g food). In control rats, no significant changes in T4 metabolism occurred during 3 days at 4°C. Urinary 125I was greatly decreased in PTU-treated rats. Exposure of these rats to cold resulted in some increase but values were still 50 % below normal. Secondly, four groups of rats were exposed to cold: control; PTU-treated; T4-treated; PTU + T4-treated. Control and T4-treated rats survived. PTU-treated rats died unless T4 was administered. Radioimmunoassay of T4 and T3 indicated significant concentrations of T3 in sera of rats from all but the PTU + T4 group. These results suggest that T4 permits survival in the cold-exposed PTU-treated rat without being converted to T3 and thus they support the concept that T4 has intrinsic biological activity.
EFFECTS OF VALINOMYCIN ON Rb+ FLUXES, ATP CONTENT AND INSULIN RELEASE IN PANCREATIC ISLETS
Authors: Idahl Lars-Åke , Sehlin Janove , Täljedal Inge-Bert , Tamarit-Rodriguez Jorge
Published: December 2008

Valinomycin, 0.5–500 nm, was tested for its effects on pancreatic islets microdissected from non-inbred ob/ob-mice. Valinomycin decreased the islet accumulation of Rb+ and the content of ATP in a dose-dependent manner; efflux of Rb+ from pre-loaded islets was not noticeably changed. Rb+ accumulation and ATP content correlated markedly; on the model of linear regression, less than 10% of the change of Rb+ accumulation in valinomycin-treated islets was statistically attributable to factors other than ATP. Valinomycin did not cause a prompt inhibition of glucose-stimulated insulin release that could reflect hyperpolarization due to increased K+ permeability. The following conclusions are drawn: 1) The plasma membranes of β-cells resemble those of neurons in having such a high ion permeability as to be relatively little influenced by valinomycin; 2) Islet accumulation of Rb+ is due to a vectorial catalyst in the plasma membrane rather than to uptake by mitochondria; 3) Rb+ accumulation in islets is ATP-dependent.
PRIMARY INTRACRANIAL HCG-PRODUCING GERMINOMA IN A BOY WITH CONGENITAL ADRENAL HYPERPLASIA
Authors: Levine L. S. , Novogroder M. , Saxena B. , Saenger P. , Saito T. , New M. I.
Published: December 2008

A primary intracranial HCG-producing tumour was studied in an 8 year old boy with congenital adrenal hyperplasia. The case provided a unique opportunity to study the sequential changes in serum and urinary androgens and HCG as measured by radioreceptor assay for HCG and by radioimmunoassay for HCG using antisera raised against the hormone specific for the β subunit of HCG. Plasma concentrations of HCG, measured by the radioreceptor assay, closely correlated with the biologic activity of his tumour, as measured by serum testosterone concentration. This case demonstrates that precocious puberty in any child, including one with a known androgen disorder such as congenital adrenal hyperplasia, warrants thorough investigation.