bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative response to oestradiol in the synthesis of the progesterone receptor in the maternal and foetal uterus of guinea pig and rabbit at the end of gestation
Authors: Laure Francoise , Pasqualini Jorge Raul
Published: December 2008

In the present paper the stimulatory effect of oestradiol on the progesterone receptor (PR) in two species: rabbit and guinea pig, is studied in both the maternal and foetal uterine tissues. Oestradiol (1 mg/kg/day) in saline solution was injected sc into the maternal compartment of pregnant guinea pig and rabbit at the end of gestation for 3 consecutive days and the PR evaluated 24 h after the last injection; control animals received the vehicle alone. In the maternal uterus the number of specific binding sites in the cytosol fraction for the synthetic progestagen R-5020 (17α,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione) in the non-treated animals was, for the rabbit 117 ± 25 (sd) fmol/mg protein and for the guinea pig 325 ± 62 (sd) fmol/mg protein. In the treated animals a stimulation is observed of 2.5–3 times, 315 ± 85 (sd) fmol/mg protein for the maternal uterus of rabbit and 865 ± 100 (sd) fmol/mg protein for the maternal uterus of guinea pig. In the foetal uterus it is a very different picture, while in the foetal uterus of guinea pig a great stimulatory effect is observed on the PR; from 267 ± 53 (sd) fmol/mg protein in the nontreated animals to 1984 ± 357 (sd) in the oestradiolprimed animals; in the foetal uterus of rabbit very little or no PR is detectable in the non-treated animals while in the treated animals with the same or 1/20 of the dose of oestradiol for only 1 day, the death of the foetus was provoked.

In summary, the effect of oestradiol on the stimulation of PR in maternal uterine tissue is similar in these two species. In the foetal uterus of guinea pig the response to the action of oestradiol on the PR is very significant but this hormone is of great toxicity for the rabbit foetus. It is concluded that the oestradiol response of the foetus is related to the maturity of the foetus.
The relationship of plasma gonadotrophins and androgen concentrations to body growth in boys
Authors: Parra Adalberto , Cervantes Carlos , Sánchez Martha , Fletes Ladislao , García-Bulnes Guadalupe , Argote Rosa Ma. , Carranco Armando , Sojo Isaura , Arias Raúl , Cortés-Gallegos Vicente
Published: December 2008

Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 alpha-hydroxyprogesterone (17α-OPH), androstenedione (Δ4) and testosterone (T) were measured in 543 healthy boys aged 6.0 to 15.9 years (with weight and height between the 3rd and 97th percentile for Mexican standards) as a function of chronologic age (CA), weight, height, surface area (SA) and calculated lean body mass (LBM) and total body fat (TBF).

The earliest hormonal event was a clear rise in plasma 17α-OHP, either prior or simultaneously to at steady increase in plasma FSH, far ahead of any sign of puberty. These changes were closely followed by a continuous rise in plasma Δ4. Thereafter, there was a prolonged period of low but progressively increasing plasma FSH levels in the face of constantly low LH levels. However, a brisk rise in plasma LH and FSH occurred at a mean weight of 35.4 kg, at a height of 144.5 cm and when LBM was 32.0 kg. Simultaneously, plasma 17α-OHP began to fall, Δ4 reached a plateau and soon after, a marked rise in plasma T was documented. When plasma LH and FSH concentrations were plotted against CA, weight, height, SA and LBM a significant quadratic equation was disclosed in each case. Both gonadotrophins did not correlate with TBF. Multiple variance analysis demonstrated that LBM and SA had the most marked effect on LH, while LBM was the most important variable affecting plasma FSH concentrations. The present data suggest the association between a "critical level" of body composition and the major hormonal events in boys, regardless of a cause-effect relationship. A critical level of LBM (20–23 kg) and not of TBF was attained at time of the initial hormonal changes, as well as at the time of the major changes in plasma gonadotrophins (32–35 kg).
Hyperprolactinaemia does not affect the development of the stimulatory mechanism of oestrogen-progesterone on LH secretion
Authors: Moguilevsky Jamie A. , Faigón María R. , Scacchi Pablo , Scwarcfarb Berta
Published: December 2008

Previous reports indicate that prolactin induces precocious puberty in the female rat. The present investigation was designed to determine if hyperprolactinaemia affects the development of the stimulatory effect of oestrogen-progesterone on LH secretion in prepubertal rats. Hyperprolactinaemia was induced by the administration of sulpiride at the dose of 7 mg/100 g body weight/day for 6 days. The rats were sacridied 6 to 9 h after the last injection. Normal sulpiride-treated rats were injected 76 h before sacrifice with 10 μg of oestradiol benzoate and with 1 mg of progesterone on the day of sacrifice. The animals were killed at 14, 22, 24, 28 and 32 days of age.

The sulpiride treatment induced a significant increase in serum prolactin levels (P < 0.01) at all ages studied. The treatment of oestrogen-progesterone induced prolactin release in controls and in the sulpiride-hyperprolactinaemic rats of 24, 28 and 32 day old but not in younger rats. The administration of oestrogen-progesterone alone in normal and in sulpiride hyperprolactinaemic rats produced a negative feed-back effect on LH secretion at 14 and 22 days of age and a significant stimulatory action at 24, 28 and 32 days. No differences were observed in the basal LH serum concentration between control and hyperprolactinaemic rats at the different ages studied. Our findings suggest that the modifications in the onset of puberty induced by hyperprolactinaemia are not connected with alterations in the maturation of the hypothalamic-pituitary mechanism involved in the positive feed-back effect of ovarian steroids on LH secretion.
The TRH-metabolite histidyl-proline-diketopiperazine (DKP) inhibits prolactin secretion in male rhesus monkeys
Authors: Brabant Georg , Wickings E. Jean , Nieschlag Eberhard
Published: December 2008

Histidyl-proline-diketopiperazine (DKP) - a stable degradation product of TRH - has been shown to selectively inhibit prolactin secretion in vitro in rat pituitary tissue. In this study the effects of DKP on serum prolactin in intact and anaesthetized male rhesus monkeys and on TRH-stimulated prolactin levels have been investigated.

In conscious monkeys 400 μg DKP significantly suppressed prolactin levels by 27%, and under ketamine anaesthesia, serum prolactin was suppressed in a dose-dependent manner by 150 and 400 μg DKP. The maximum prolactin response and the cumulative response to TRH (20 μg) was significantly and specifically inhibited by 400 μg DKP, while the lower dose was without effect. TSH levels were not affected by DKP in any instance.

Hence DKP can specifically inhibit prolactin release in the rhesus monkey, and may be discussed as a possible regulatory factor in prolactin secretion.
Thyroglobulin assay in the follow-up of patients with differentiated thyroid carcinomas: comparison of its value in patients with or without normal residual tissue
Authors: Schlumberger M. , Fragu P. , Parmentier C. , Tubiana M.
Published: December 2008

The usefulness of serum thyroglobulin (Tg) assay in the follow-up of differentiated thyroid carcinomas has been evaluated in 109 subjects divided into two groups.

Group 1 included 64 patients who had undergone total thyroid ablation. In 40 of the 41 patients in complete remission serum Tg was undetectable during replacement therapy (TSH below 5 μU/ml). In 18 out of the 40 patients serum TG was detectable following endogenous TSH stimulation. As 83% of these patients had ectopic uptake prior to the last radioiodine treatment, this release of Tg under TSH stimulation suggests the persistence of occult neoplastic tissue. Of the other 23 patients, 20 had bone or lung metastases and 3 patients had lymph node recurrences: in all these patients, serum Tg was detectable during replacement therapy and increased after TSH stimulation.

Group 2 included 45 patients in whom normal residual thyroid tissue was present at the time of the investigation. Of these, 35 patients were in apparent remission and 19 of them had detectable Tg level within the normal range. The other 10 patients had detectable metastases and in 4 of these the Tg level was also within the normal range. Thus, no conclusion can be drawn from a normal Tg level in the presence of residual thyroid tissue. Bovine TSH stimulation did not improve significantly the diagnostic value of Tg assay in this group of patients.
hCG and hCG subunits as tumour markers in patients with endocrine pancreatic tumours and carcinoids
Authors: Öberg Kjell , Wide Leif
Published: December 2008

Serum levels of hCG, hCG-α- and hCG-βsubunits were measured in 29 patients with APUD-tumours, 16 patients with endocrine pancreatic tumours (EPT) and 13 patients with carcinoids. Twenty out of 29 patients (69%) had elevated level of hCG and its subunits. Among patients with EPT, 11 out of 16 (69%) had rised levels of these peptides. Three patients with benign tumours had normal concentrations, thus giving a frequency of 85% in the group of malignant EPT. In patients with carcinoids 9 out of 13 (69%) had elevated serum levels of at least one of the components. A discordance in secretion pattern between the two types of APUD-tumours was noticed. Only one patient, a case with a carcinoid had rised levels of the complete hCG molecule. The levels of hCG-α were elevated in 23% of the patients with malignant EPT and 69% of the patients with carcinoids while the corresponding frequencies of raised hCG-β levels were 69% and 8%, respectively. Three out of 4 patients with so-called non-functioning islet cell tumours had rised levels of the subunits. These results indicate that hCG subunits are valuable tumour markers in both of these APUD-tumours, and that malignant EPT predominantly secrete hCG-β- and carcinoids hCG-α-subunits.
Characterization of cytoplasmic progesterone receptors in rat granulosa cells. Evidence for nuclear translocation
Authors: Naess Oddvar
Published: December 2008

The granulosa cells from immature rats were found to possess binding components for progestins. The physicochemical properties were determined. By sucrose gradient centrifugation, binding of [3H]R-5020 was observed in the 7S and 4S region of the gradient. Isoelectric focusing, however, revealed only one binding component (pH 5.9). The component was of protein nature and was destroyed by heating the cytosol fraction to 37°C for 30 min. Scatchard analysis of the data showed one single binding component with high affinity (KD ∼ 1.5 × 10−9 mol/l). The binding capacity was 50 fmol/mg protein in unprimed animals and 193 fmol/mg protein in animals treated with oestrogen. Studies on the steroid specificity revealed that R-5020 had the highest affinity for the receptors, followed by progesterone and the synthetic progestin, cyproterone acetate. Corticosterone, oestradiol-17β and testosterone had low affinity, whereas cortisol had no significant affinity for the receptor.

Using exchange assay, it was demonstrated that the cytoplasmic receptors translocated to the nucleus after administration of unlabelled progesterone to the animals.

The presence of cytoplasmic and nuclear progestin receptors, strongly indicates that progesterone may have a direct effect on granulosa cell function.
The effect of sex steroids on the degradation of LRH by hypothalamic homogenates
Authors: Tate Anna C. , Swift A. D.
Published: December 2008

Extract of hypothalami was prepared which contained peptidase capable of degrading LRH. The degradation of LRH by this extract either alone or under the influence of oestrogens, androgens and cholesterol, when added to the extract was measured. Oestrone, oestradiol and oestriol (1 pg to 100 pg) stimulated mean peptidase activity significantly (P< 0.001) in a dose-dependent manner. Testosterone (0.1 ng to 10 ng) also caused a dose-dependent increase in degradation of LRH, the two highest doses used significantly increasing the mean activity (P < 0.001). Only the highest dose of androstenedione (10 ng) or dehydroepiandrosterone (10 ng) caused a significant increase of the mean LRH degradation (P < 0.05). Neither cholesterol nor dihydrotestosterone increased peptidase activity when added to the extract.

It is suggested that it is possible that these peptidase enzymes could occupy a role in the negative feedback of steroids on the hypothalamus.
Effects of bromocriptine-induced pregnancy on prolactin-secreting pituitary tumours
Authors: Bergh T. , Nillius S. J. , Larsson S.-G. , Wide L.
Published: December 2008

Twenty-eight women with hyperprolactinaemia and amenorrhoea received bromocriptine treatment which resulted in 31 term pregnancies. Bromocriptine treatment was stopped as soon as pregnancy was established. Nineteen of the women had radiological signs of a pituitary tumour. The pregnancies were clinically un-eventful in all cases except one who developed headache. Post-partum sellar X-ray showed pregnancy-induced enlargement of the pituitary fossa in 4 of the 28 women. Regression of the radiological changes occurred in 3 of the 4 women within 2 years after the delivery. The women with abnormal sellar X-rays had no difference in the mean prolactin levels before treatment and after pregnancy and lactation while all the women with normal sellae had lower prolactin levels after pregnancy than before. Three women resumed regular spontaneous menstruations after pregnancy and lactation but only one conceived again.

Thus, serious pituitary tumour complications are rare in hyperprolactinaemic women with bromocriptine-induced pregnancies. The pregnancy does not worsen the condition. Resolution of hyperprolactinaemia after bromocriptine-induced pregnancy is an unfrequent finding.
Characterisation of the cyclic AMP response to thyrotrophin in monolayer cultures of normal human thyroid cells
Authors: Bidey Stephen P. , Marshall Nicholas J. , Ekins Roger P.
Published: December 2008

The cyclic AMP response to thyrotrophin (TSH) has been investigated in cells prepared from human thyroid tissue obtained during surgery for sub-total laryngectomy, and maintained under in vitro conditions as primary monolayer cultures.

When cells were incubated with 1.0 mU TSH/ml, a maximal level of intracellular cyclic AMP was reached after 20 min of incubation in the presence of 0.5 mm 3-isobutyl-1-methyl xanthine (MIX). This level of cyclic AMP was sustained for at least 2 h. Half-maximal stimulation of cyclic AMP was produced by TSH doses of between 1 and 5 mU/ml. In a study of a series of eight groups of monolayer cultures, each derived from a single, different thyroid gland, the mean stimulation of cyclic AMP given by 50 mU TSH/ml was 37.8-fold greater than in non-stimulated cell monolayers.

Significant stimulation to 50 μU TSH/ml was observed in some monolayers and the precision of measurement of TSH was better than 15% over the TSH dose range 0.2–1.0 mU/ml. The magnitude of the cyclic AMP response to TSH was unaffected by the presence in the incubation medium of 20% (v/v) normal human serum. A cyclic AMP response to TSH was still demonstrable in cells that had been maintained for a period of 22 days in monolayer culture, although the response was reduced in comparison with that given by 4–5 day old cultures.
A new protease in hog thyroid lysosomes
Authors: Nakagawa H. , Endo Y. , Ohtaki S.
Published: December 2008

A leupeptin-sensitive new protease was partially purified from hog thyroid lysosomes. The purification procedure included solubilization by hypotonic treatment of lysosomes, and Sephacryl S-300 and Sephadex G-100 gel chromatography, and the purification ratio was 10-fold from lysosomes. The pH optimum of the protease activity was around 5.5 and its molecular weight was estimated to be 22 000 by gel filtration. 2-Mercaptoethanol activated the hydrolysis of protein substrates and its effect was most pronounced in the case of thyroglobulin as substrate. Among the inhibitors used, leupeptin, antipain, toluenesulfonyl-lysine chloromethyl ketone and, to a lesser degree, chymostatin and toluenesulfonyl-phenylalanine chloromethyl ketone effectively inhibited the hydrolysis of casein by the enzyme at pH 5.5, whereas pepstatin did not inhibit the activity significantly. The enzyme activity was also inhibited by sulfhydryl inhibitors such as iodoacetamide, p-chloromercuribenzoate, and N-ethylmaleimide.

The release of iodoamino acids from thyroglobulin by the enzyme was inhibited in the same manner by the inhibitors used in the hydrolysis of casein.

The physiological role of the new protease is discussed in comparison with cathepsin B and L found in liver lysosomes.
The relation between catecholamines, glucagon and pancreatic polypeptide during hypoglycaemia in man
Authors: Järhult Johannes , Farnebo Lars-Ove , Hamberger Bertil , Holst Jens , Schwartz Thue W.
Published: December 2008

The effects of insulin hypoglycaemia (0.15 IU/kg) on plasma adrenaline, noradrenaline, dopamine, glucagon and pancreatic polypeptide (PP) concentrations were investigated in 6 adrenalectomized subjects and 6 healthy controls. Both the rise in mean plasma insulin and the fall in mean blood glucose concentration were closely similar in the two groups. Mean plasma adrenaline concentration rose by about 3 nmol/l in the normal subjects, but remained unchanged in adrenalectomized subjects. Mean plasma noradrenaline concentration increased by about 2 nmol/l in both groups. Despite the large difference in adrenaline concentrations during hypoglycaemia, there was no significant difference between the responses of the endocrine pancreas of the normal and adrenalectomized subjects. Thus, mean plasma glucagon concentration rose by about 30 pmol/l and mean plasma PP concentration by about 150 pmol/l in each group. We conclude that the release of glucagon and PP during hypoglycaemia does not depend upon changes in plasma adrenaline concentration in man.
Insulin hypoglycaemia in normal and adrenalectomized subjects: comparison of metabolic parameters and endocrine counter regulation
Authors: Altorfer R. M. , Ziegler W. H. , Froesch E. R.
Published: December 2008

Insulin tolerance tests were carried out in normal subjects and in adrenalectomized (ADX) patients in order to better understand the importance of counter regulatory hormones for the recovery from hypoglycaemia.

Compared to normal subjects recovery of plasma glucose and of free fatty acid levels in adrenalectomized patients is retarded. The levels of glucagon are significantly higher in ADX patients during rest than in normal subjects. As expected, epinephrine and norepinephrine levels did not increase in ADX patients and, accordingly, blood pressure did not change. Growth hormone levels were the same in both groups of subjects. Interestingly, there was no clear-cut difference with regard to subjective symptoms of hypoglycaemia.

It would appear that epinephrine is important for the rapid initial recovery from hypoglycaemia, whereas other hormones play a more important role later on.
Biomechanical changes in connective tissues induced by experimental diabetes
Authors: Andreassen T. T. , Seyer-Hansen K. , Oxlund H.
Published: December 2008

The biomechanical properties of skin and aorta were studied in rats with experimental (streptozotocin) diabetes.

After 30 days of diabetes the collagen content of the skin was diminished by 30%.

By biomechanical testing collagen from diabetic rats was found to exhibit increased stiffness and strength: maximal stiffness was increased by 20% and the strain at maximum stress was decreased by 10%.

Insulin treatment prevented all changes.

No differences were found between aortic specimens from diabetic and normal rats.
Regulation of prolactin and thyrotrophin secretion during human pregnancy: effect of sulpiride and TRH administration
Authors: Ylikorkala Olavi , Kivinen Seppo , Viinikka Lasse
Published: December 2008

The regulation of prolactin (Prl) and thyrotrophin (TSH) secretions during early human gestation was studied in 30 healthy women. Twelve women were treated with oral sulpiride, 150 mg daily for two weeks, and the Prl and TSH responses to 220 μg of iv thyrotrophin-releasing hormone (TRH) were measured before and at the end of sulpiride administration. Eight women were given 200 mg of sulpiride im, and 4 of them received 200 μg of TRH 30 min later. In 4 women the order of the TRH and sulpiride injections was reversed. Six women were studied as controls.

Oral sulpiride treatment induced a significant Prl elevation from 14.6 ± 1.8 μg/l (mean ± sem) to 83.0 ± 4.0 μg/l, whereas the mean TSH levels did not change. Before sulpiride intake, TRH caused a mean maximal increment of 42.9 ± 4.7 μg/l in the Prl levels and an increment of 5.6 ± 0.9 IU/l in the TSH levels. During sulpiride administration, TRH caused a mean maximal increment of 16.5 ± 4.7 μg/l in the Prl levels and 3.5 ± 0.6 IU/l in the TSH levels. Both responses were significantly smaller (P < 0.001) during the sulpiride treatment than before.

Intramuscular injection of sulpiride raised the mean Prl concentration by 282 ± 32 μg/l (P < 0.001) and the mean TSH concentration by 0.5 ± 0.1 IU/l (P < 0.05). The Prl elevation was 502 ± 109 μg/l when sulpiride was injected after TRH. A preceding im sulpiride injection caused no changes in Prl and TSH responses to TRH.

These results show that in addition to Prl also TSH secretion is partially controlled by the dopaminergic system during early human pregnancy.
No proof of anorectic properties of pGlu-His-Gly in rats and mice
Authors: Knuth U. A. , Spiegelburg K. , Schneider H. P. G.
Published: December 2008

Two groups of 7 rats were injected sc with 10 μg/d and 100 μg/d of pGlu-His-GlyOH or the same volume of saline for 20 days. No differences in body weight or food consumption could be detected during two months of observation.

The same negative results were obtained when 4 groups of 10 mice were treated with 0.17 μg/d pGlu-His-GlyOH or saline.
Regulation of humoral immunity in rats by pituitary hormones
Authors: Berczi Istvan , Nagy Eva , Kovacs Kalman , Horvath Eva
Published: December 2008

Hypophysectomized female Fischer 344 and Wistar-Furth rats had severely impaired primary and secondary antibody responses to sheep red blood cells (SRBC). Mercaptoethanol-sensitive (IgM) and mercaptoethanol-resistant (IgG) antibodies were similarly affected. Titers to E. Coli 055:B5 lipopolysaccharide were also significantly decreased in such animals. The antibody response of hypophysectomized rats could be restored by syngeneic pituitary grafts when placed under the kidney capsule or by prolactin treatment. Growth hormone was less effective in this respect than prolactin. Treatment of normal rats with ACTH suppressed their antibody formation to SRBC. These results indicate that the pituitary gland has the potential to regulate humoral immune responses.
Radioimmunoassay of canine growth hormone
Authors: Eigenmann J. E. , Eigenmann R. Y.
Published: December 2008

A sensitive radioimmunoassay (RIA) for canine growth hormone (GH) was developed. Antibodies were elicited in rhesus monkeys. One antiserum exhibited a working titer at a dilution of 1:500000. Radioiodination was performed enzymatically employing lactoperoxidase. Logit-log transformation and least squares fitting resulted in straight line fitting of the standard curve between 0.39 and 50 ng/ml. Formation of largemolecular [12SI]GH during storage caused diminished assay sensitivity. Therefore [125I]GH was re-purified by gel chromatography. Using this procedure, high and reproducible assay sensitivity was obtained. Tracer preparations were used for as long as 3 months after iodination. Diluted plasma from normal and acromegalic dogs resulted in a dose-response curve parallel to the standard curve. Canine prolactin exhibited a cross-reactivity of 2%. The within-assay coefficient of variation (CV) was 3.8 and the between-assay CV was 7.2%. Mean plasma GH concentration in normal dogs was 1.92 ± 0.14 ng/ml (mean ± sem). GH levels in acromegalic dogs were appreciably higher. Insulin-induced hypoglycaemia, arginine and ornithine administration resulted in inconsistent and sluggish GH increment. A better response was obtained by injecting a low dose of clonidine. Clonidine administration to hypopituitary dogs resulted in absent or poor GH increment.
Propranolol and the hypercalcaemia of thyrotoxicosis
Authors: Feely John
Published: December 2008

The effect of propranolol on serum calcium was studied in 25 patients with thyrotoxicosis including 5 with hypercalcaemia. In patients with hypercalcaemia iv propranolol significantly reduced serum calcium. Oral therapy 160 mg/day reduced calcium non-significantly from 2.72 ± 0.09 (mean ± SD) to 2.59 ± 0.13 mmol/l, however on 320 mg/day the reduction (to 2.5 ± 0.15 mmol/l) was significant. In normocalcaemic patients oral propranolol did not influence serum calcium. Both in hyper- and normocalcaemic thyrotoxic patients propranolol increased (P < 0.01) serum phosphate.
Some unexpected effects of thyrotrophin on the metabolism of thyroid cells isolated from non-toxic goitre
Authors: Wadeleux P. A. , Winand R. J.
Published: December 2008

In cultured cells of normal dog thyroid, thyrotrophin (TSH) has been shown to have a mitogenic effect. The present study suggests an opposite action in cells from human non-toxic goitre. After incubation of these cells with [3H]thymidine, a decreased incorporation into DNA is observed in the presence of TSH.

Whereas in dog thyroid cells the hormone enhances the incorporation of [3H]leucine and [14C]glucosamine into macromolecules, TSH inhibits the incorporation by human non-toxic goitre cells. Polyacrylamide gel electrophoresis analysis of the proteins present in the cell layer or released in the culture medium shows that the inhibition affects all the newly synthesized peptides, including the radioactive material co-migrating with the major band (330 000 daltons) observed with human purified thyroglobulin.

While several hydrolase activities are not influenced by TSH in dog thyroid cells, the hormone markedly decreases the activities of some hydrolases of thyroid cells from human non-toxic goitre.

Our results therefore suggest that, in cultured thyroid cells from human non-toxic goitre, TSH induces a resting state of the cells, characterized by reduced growth, reduced protein synthesis and reduced thyroglobulin hydrolysis.
Influence of medroxyprogesterone acetate (Provera) on plasma growth hormone levels and on carbohydrate metabolism
Authors: Eigenmann J. E. , Rijnberk A.
Published: December 2008

Six elderly ovariohysterectomized dogs were given medroxyprogesterone acetate (MPA 10 mg/kg body weight) at 3 week intervals in a total of 5 injections. Mean growth hormone (GH) levels increased significantly after the third injection, continued to increase slightly after the fourth and fifth injections and remained significantly elevated over control levels as late as 16 weeks after the last MPA administration (P < 0.05). The mean glucose concentrations during iv glucose tolerance tests (IVGTT) were significantly elevated at 30, 45 and 60 min after a glucose load when performed after the third MPA injection. Following the second MPA injection, mean insulin levels were significantly elevated at rest, 30 and 45 min after glucose load. After the fourth and fifth MPA injections, mean insulin levels during IVGTT were significantly elevated at 30 min only.

These findings denote that (1) after a lag phase of several weeks MPA induces moderate GH increase in ovariohysterectomized dogs; (2) MPA administration causes moderate disturbance of glucose homoeostasis.
LH pattern in ovariectomised rats after continuous blood withdrawal: effects of different substitutions
Authors: Schneider H. Th. , Kraft K. , Breuer H.
Published: December 2008

Plasma concentrations of LH and of sodium, potassium, total protein and haemoglobin were measured in ovariectomised rats during continuous blood withdrawal up to 180 min; 0.45 ml blood samples were taken every 10 min, the total volume of blood removed not exceeding 9 ml. Four groups of animals were studied: group A received no substitution (controls), group B was substituted with 0.9% NaCl-solution, group C with 3.5% polypeptide solution (Haemaccel), and group D with a suspension of washed erythrocytes from the blood removed. During blood withdrawal, the mean values of LH concentrations as well as the amplitudes of the rhythmic LH pulses remained constant in all the animals. However, the rate of pulses was reduced in the control animals and in the group receiving 0.9% NaCl-solution during the period between 90 and 180 min; in contrast no change was observed in the groups C and D during the whole period. The results presented here show that the characteristic LH pattern in ovariectomised rats is not affected by volume depletion, provided the blood is replaced by a solution containing either a polypeptide or a suspension of washed erythrocytes.
Effect of alloxan diabetes on kidney growth in intact and castrated mice
Authors: Broulik P. D. , Schreiber V.
Published: December 2008

The mouse kidney is particularly responsive to the withdrawal or administration of androgens. The absence of endogenous androgens after castration led to decreased RNA synthesis and subsequent decrease in weight of the kidney. The induction of diabetes in 21 days castrated mice restored kidney weight. In intact mice made diabetic by iv injection of alloxan there was a increase in kidney weight. This increase was accompanied by a proportional inacrease in RNA. In mice hypertrophy was found to be the major factor in renal growth. When castration and diabetes were combined kidney weight did not fall as in the case of castration only but increased even above the kidney weight of intact animals. There was a parallel rise in RNA content of the kidney. Castration does not inhibit the renotrophic activity of alloxan diabetes in mice. Renal growth in alloxan diabetes is quite independent of the presence of androgens.
Ontogeny of gastric inhibitory peptide in the human gastro-intestinal tract and endocrine pancreas
Authors: Leduque P. , Gespach C. , Brown J. C. , Rosselin G. , Dubois P. M.
Published: December 2008

The appearance and distribution of the gastro-intestinal hormone, gastric inhibitory peptide (GIP) were examined in the gastro-entero-pancreatic system of human foetuses, aged 5–24 weeks, by immunocytochemistry or radioimmunoassay. The first immunoreactive cells were observed in the gut from 16 weeks of gestation. The GIP-containing cells were localized preferentially in the villous epithelium of the small intestine. In the radioimmunoassay, the highest concentrations of immunoreactive GIP (IR-GIP) were detected from 13 to 21 weeks of gestation. The tissue concentration of IR-GIP was 68.10 ± 10.70 ng/g wet weight of duodenum, 30.29 ± 3.96 ng/g wet weight of jejuno-ileum and 3.05 ± 1.97 ng/g wet weight in the colon. Measurable amounts of IR-GIP (4.93 ± 1.57 ng/g wet weight of organ) were found from 9 to 12 weeks in the jejuno-ileal region. The ontogenic development of IR-GIP was studied in this region. From 13 to 21 weeks of gestation, the IR-GIP content per g of organ increased about 6-fold. In the endocrine pancreas, GIP antiserum No. R07 was potent in staining A cells from 14 weeks of gestation. In radioimmunological tests, no cross-reactions of the anti-GIP sera R 07 and GP 01 with heterologous peptides were observed. Labelling of paraffin and semi-thin sections was subjected not only to the usual specificity tests, but also to particularly extensive cross-reaction studies. GIP-like immunoreactivity was not inhibited by absorptions against heterologous peptides added at varying concentrations. The immunocytological and radioimmunological results are consistent with an eventual implication of GIP in the endocrine regulation of metabolism or in the development of the gastro-entero-pancreatic system during the intrauterine life in man.
In vitro inhibition of trophoblast maturation and expansion of early rat blastocysts by an oestrogen antagonist
Authors: Roy S. K. , Sengupta J. , Paria B. C. , Manchanda S. K.
Published: December 2008

Rat blastocyst development and expansion were studied in an in vitro culture system. Early blastocysts collected from rats on the morning of day 5 were shown to develop normally and underwent expansion when placed in bovine serum albumin supplemented culture medium for 12 h at 37°C. Nafoxidine, an oestrogen antagonist, prevented embryo expansion when added to the culture medium, and it was found that if oestradiol-17β was added to this medium this inhibitory effect was removed and the embryos again expanded. Ethanol, used as a solvent for steroids, and cholesterol were added to the medium containing nafoxidine but the blastocysts still remained unexpanded after 12 h in culture. These results suggest a need for oestrogen action during blastocyst expansion in vitro. Cultured rat blastocysts were subjected to histochemical study for acid phosphatase (ACPase) and leucylnaphthylamidase (LNAse). In unexpanded blastocysts ACPase was found to be low while LNAse activity was higher when compared with enzyme distribution patterns in expanded blastocysts.
Growth hormone secretion in pubertal and adult subjects
Authors: Minuto Francesco , Barreca Antonina , Ferrini Silvano , Mazzocchi Giancarlo , Del Monte Patrizia , Giordano Giulio
Published: December 2008

GH responsiveness to insulin-induced hypoglycaemia and its circadian secretion were studied in a group of subjects in different pubertal stages.

The GH peak after insulin was minimal in stage 1 boys (7.6 ± 1.3 (sem) ng/ml) and increased progressively, in parallel with pubertal maturation, reaching a maximum in the adult state (20 ± 4.0 ng/ml); the basal value was superimposable in all groups studied.

The circadian secretion showed a sleep-related surge which was almost identical in the different stages; however in pubertal stage 1 boys multiple secretory peaks were observed, mainly during waking hours. A statistically significant difference (P < 0.05) was observed in the mean concentration recorded during the day with a maximum in stage 1 boys (2.7 ± 0.2 ng/ml) and a gradual decrease to a minimum in adults (1.2 ± 0.3 ng/ml).

This pattern seems to suggest that a pulsatile rhythm is present in boys, similar to that observed for gonadotrophins.
Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency
Authors: Zachmann M. , Tassinari D. , Sorgo W. , Exner G. U. , Kempken B. , Prader A.
Published: December 2008

Twentythree boys with delayed adolescence (age 15.7 ± 2.0, bone age 12.4 ± 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirtyseven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 ± 8 μg/m2/12 h) and 13 with an insufficient (191 ± 16 μg/m2/12 h) THS response. Values in the second and third sample were higher, indicating a dealyed response. In 12 tests (group B), the results were normal (1016 ± 143 μg/m2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age.

The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.
Kinetics of LRH-induced LH-release in vivo: influence of LRH pre-treatment
Authors: Koiter T. R. , Pols-Valkhof N. , Schuiling G. A.
Published: December 2008

The influence of an LRH injection (50 ng/ 100 g b.w.) on the LH-response to a second, equally large LRH injection or a constant rate infusion of LRH (104 ng/h), administered 1 h later, was studied in phenobarbitone-anaesthetized, oil- or oestradiol benzoate (OeB)-treated rats ovariectomized (OVX) 5 weeks earlier. From the plasma LH concentration the mean maximal LH secretion rates, as well as the amounts of LH secreted, were calculated on the basis of a one-compartment model, proceeding from a half-life of LH of 15 min.

In both the oil- and the OeB-treated animals, not only the mean maximal LH secretion rate, but also the amount of LH secreted during the first hour following the injection, was significantly higher after the second LRH injection than after the first one (LRH self-priming effect). Infusion of LRH in LRH-primed OVX rats revealed that the LH secretion accelerates immediately after the start of the infusion and this acceleration lasts about 1 h. In the saline-injected controls, on the other hand, the LH secretion, although elevated, remains constant during the first 30 min of LRH infusion and accelerates only thereafter during about 1 h. Yet, maximal LH secretion rates are not statistically different between the LRH-primed oil- or OeB-treated OVX rats and their respective saline-injected controls.

It is concluded that the self-priming effect of LRH does not lead to an increase of the ultimate maximal LH secretion rate. Rather, during priming the conditions necessary for immediate acceleration of the LH secretion rate are established, and priming thus causes a shift in time, that is, an advancement, of the LH-response to a subsequent LRH stimulus.
TSH and TSH-subunit production by human thyrotrophic tumour cells in monolayer culture
Authors: Filetti S. , Rapoport B. , Aron D. C. , Greenspan F. C. , Wilson C. B. , Fraser W.
Published: December 2008

Studies were performed on pituitary adenoma tissue obtained from a patient with hyperthyroidism secondary to inappropriate thyrotrophin (TSH) secretion. Cells dispersed enzymatically were established in primary monolayer culture for a period of 39 days. Intact TSH and TSH-subunit release into the culture medium declined over the initial 20 days, followed by a rebound in TSH and β-TSH production until the time of subculture at day 39. In vitro α-TSH production declined more slowly than did TSH and β-TSH, but did not recover in parallel with intact TSH. Production of α-TSH by cultured cells, at different times, was 20–80-fold greater than that of β-TSH. In the pituitary tissue α-TSH content (112 ng/mg tissue) was 8.6-fold greater than the β-TSH concentration (13 ng/mg tissue), but similar to intact TSH content (105 ng/mg tissue). In serum, the α-TSH concentration (6.5 ng/ml) was lower than in most previously reported patients with thyrotrophic adenomata. TSH bioactivity in tumour tissue (approximately 600 ng/mg tissue) was greater than the immunoreactive TSH concentration. LH, FSH and prolactin were undetectable in tumour tissue, and in the culture medium throughout the period of cell culture. Exposure of thyrotroph monolayers to 10−6 m TRH for 4 h led to 32%-– 600% increases in TRH release, depending on the day of culture and the cell flask utilized. The α-TSH response to TRH paralleled that of intact TSH, β-TSH being unmeasureable. Incubation of cell monolayers for 4 h in 5 × 10−7 m dopamine decreased TSH and α-TSH secretion into the medium. In contrast, exposure of cells to T3 at concentrations as high as 10−6 m did not affect TSH secretion. Surprisingly, TRH (10−7 m to 2 × 10−6 m) inhibited cultured thyrotroph cAMP content by about 50%; cGMP levels were unaffected.

This study, the first to examine secretory function of human thyrotrophic tumour cells in vitro, confirms the disproportionate production of α-TSH by these tumours, even though this may not be apparent from the level of the α-subunit in serum. The data indicate that TSH secretion by thyrotroph tumour cells, at least from this particular patient, remains sensitive to TRH stimulation and dopamine inhibition, but insensitive to inhibition by T3. Not all TSH bioactivity is reflected by the immunoassayable TSH concentration, suggesting that the tumour may be producing variants of normal TSH that nevertheless retain biological activity. Finally, the data suggest that, at least in this particular tumour, TRH stimulation of TSH secretion is not mediated by cAMP as a second messenger.
Dexamethasone suppressible hyperaldosteronism in a child with nephrosclerosis
Authors: Lee Stanley M. , Lightner Elmer , Witte Marlys , Oberfield Sharon , Levine Lenore , New Maria I.
Published: December 2008

A 9 year old Mexican boy presented with severe hypertension, hypokalaemia and features suggesting acute glomerulonephritis. Nephrosclerosis was present on renal biopsy. Aldosterone levels were unresponsive to variations in dietary salt intake and plasma renin activity was suppressed. Following oral dexamethasone therapy (2 mg/day), plasma aldosterone decreased to undetectable levels, serum potassium normalized and plasma renin activity gradually increased. Dexamethasone also restored the normal responsiveness of the renin-aldosterone system to postural stimuli.

The patient exhibited a marked response to a single dose of ACTH with a rise in plasma aldosterone. Long-term blood pressure control and normal potassium levels have been achieved with oral prednisone therapy (5 mg/day) for a period of one year. This case of dexamethasone suppressible hyperaldosteronism (DSH) illustrates that the degree of hypertension in this syndrome may produce severe renal microvascular lesions. DSH should be considered in all children who present with low renin hypertension.
Rat placental hormones: attempts for identification of rat chorionic gonadotrophin and rat placental lactogen by in vivo experiments
Authors: Tabarelli Marco , Kofler R. , Schwarz S. , Wick G.
Published: December 2008

Rat placental extracts (rPE) were investigated in bioassays for their possible content of rat placental lactogen (rPL) and rat chorionic gonadotrophin (rCG). Luteotrophic and lactogenic activity of rPL was assessed by substitution of rats depleted of endogenous prolactin (Prl) by means of bromoergocryptine (BEC) in early pregnancy and the period of lactation, respectively. The abortifacient effect of a single dose of BEC on day 6 of pregnancy was abolished by rPE equivalent to 1 g rat placenta corresponding to 5 IU bovine Prl (NIH-P-B 2). Substitution was necessary until the evening of day 7 indicating that rPL does not take over the function of Prl before day 8. During lactation rPE reversed the lactation inhibiting effect of daily BEC treatment. In this assay rPL activity corresponded to 1.25–2.5 IU bPrl/g placenta.

In order to test for the possible existence of rCG the gonadotrophic activity of rPE was assessed in immature female mice. No gonadotrophic activity was found when rPE equivalent to 1 g rat placenta was administered, whereas equivalents of 3 mg human placenta and 12 mg rat pituitary entailed a dose-dependent response. In this system 0.12 IU human chorionic gonadotrophin (hCG), which served as standard, was the minimal dose (MD) resulting in increased uterine weight.

In addition rPE was tested in the immature female rat, where the limit of detection was found to be 0.5 IU hCG. Again no gonadotrophic activity was found in rPE. As the effects of rCG might have been restricted to its presumed target, the corpus luteum of pregnancy, rPE was also tested in pregnant rats depleted of endogenous luteinizing hormone (LH) by a single injection of anti-LH antibodies on day 10 of pregnancy. A MDof 0.5 IU hCG, which served as standard, prevented resorption of foetuses in all animals tested. rPE equivalent to 3.5 g rat placenta, rat pregnancy serum of day 18 and placental transplants could not substitute for endogenous LH.
Pharmacokinetics of norethindrone acetate in women after the insertion of a single subdermal implant releasing norethindrone acetate
Authors: Singh Harbans , Uniyal J P , Jha P , Takker D , Murguesan K , Hingorani V , Laumas K R
Published: December 2008

The metabolic clearance rate (MCR) of norethindrone acetate1 (NETA) and norethindrone (NET) levels in plasma were studied after an iv injection of [3H]NETA in three women before and at 1 week, 1, 2 and 6 months following the insertion of a single silastic subdermal implant releasing microquantities of NETA. No significant change in the MCR of NETA was observed at 1 week (459 ± 72 1/day), 1 month (489 ± 113 1/day) and 2 months (522 ± 144 1/day) compared with that of control (525 ± 108 1/day). However, MCR of NETA showed significant increase in women exposed to continuous presence of NETA for a period of 6 months (608 ± 121 1/day; P < 0.025). NETA was rapidly and extensively metabolized into NET. At 1 week, 1, 2 and 6 months of study, NET was observed to be present in higher amounts compared with NETA. The production rate (PR) of progesterone decreased significantly at 2 and 6 months of NETA implant insertion compared with the PR before the insertion of implant.
Effect of opioid peptides on gonadotrophin secretion
Authors: Motta M. , Martini L.
Published: December 2008

The intraventricular injection of 25 μg of Methionine-Enkephalin (Met-Enk) induces a significant increase of serum LH levels in long-term ovariectomized rats 15, 30 and 60 min following administration. The synthetic Met-Enk agonistic analogue [D-Ala2]Methionine-Enkephalinamide ([D-Ala2]Met-Enk) also enhances significantly serum LH levels at 30 and 60 min; under the same experimental conditions neither Met-Enk nor [D-Ala2]Met-Enk modifies serum levels of FSH following intraventricular injections into ovariectomized animals. It is concluded that, under particular circumstances, opioid peptides of the Met-Enk family may stimulate LH release.
Plasma gonadotrophins profile in relation to body composition in underprivileged boys
Authors: Parra A. , Ramos-Galván R. , Cervantes C. , Sánchez M. , de la Vega M. A. Gálvez
Published: December 2008

The plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured in 250 underprivileged boys (UP boys) aged 9.0 to 15.9 years living in a State orphanage and in 357 clinically healthy boys of the same age (with weight and height between the 3rd and 97th percentile for Mexican standards) and correlated with chronological age (CA), weight, height and calculated lean body mass (LBM) and total body fat (TBF). On a group basis, UP boys had a 2 years delay in the onset of clinical signs of puberty as well as a mild degree of malnutrition. In both groups of boys, the mean weights at time of initiation of the adolescent growth spurt in weight and at time of peak velocity of weight gain were very close to each other and similar to the values reported for Caucasian boys. The same phenomenon was true for their heights and the amounts of LBM and TBF (whether as an absolute value or as a percentage of body weight). Based on CA mean plasma FSH concentrations in UP boys were lower than normal from 11.0 to 13.9 years and the subsequent steep rise of this hormone occurred 2 years later than in healthy boys; however, when analyzed as a function of body weight, height or LMB, no such quantitative or qualitative differences emerged. On the other hand, mean plasma LH concentrations in UP boys were higher than in healthy boys only up to certain CA (< 12.9 years), weight (< 42.9 kg), height (< 147.0 cm), LBM (< 35.0 kg) or TBF (< 9.0 kg); however, no steep rise in plasma LH was observed in contrast to healthy boys. Therefore, although from a chronologic view point UP boys had a delayed onset in plasma gonadotrophins changes, they did occur in association with the attainment of similar weight, height and LBM as in healthy boys. This observation seems to support further the hypothesis of a close association between a 'critical' level of LBM (and not body fat) and the initiation of puberty, both in healthy and multiply deprived boys.