bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF CYCLOHEXIMIDE ON THE ULTRASTRUCTURE OF THE ZONA FASCICULATA OF THE YOUNG RAT ADRENAL
Authors: Magalhães Maria C. , Resende C. , Magalhães M. M.
Published: December 2008

The ultrastructural changes induced in the cells of the young rat adrenal zona fasciculata by cycloheximide are studied. Thirty minutes after administration of doses producing inhibition of protein synthesis (1.5 and 4.5 mg/kg body weight) there was a significant increase in the relative volume of the nucleolus, as shown by stereologic methods, which was accompanied by extensive perinucleolar chromatin caps. In the cytoplasm, membranous whorls were observed in several organelles and the background cytoplasm, but the volume fractions of the organelles were not significantly altered. Nucleolar changes were interpreted as suggesting that the inhibition of cytoplasmic protein synthesis may be accompanied by an enhanced formation of nucleolar proteins.
USE OF HPLC TO DETERMINE THE EFFECT OF 17β-HYDROXY-7α-METHYLANDROST-5-EN-3-ONE (RMI 12,936) ON PRODUCTION OF PROGESTERONE BY RAT OVARIAN HOMOGENATE
Authors: Taylor R. B. , Kendle K. E.
Published: December 2008

A new high pressure liquid chromatography (HPLC) method for the determination of progesterone in the presence of other Δ43-ketosteroids is described. Using this method it is shown that the rate of production of progesterone from pregn-5-ene-3,20-dione by rat ovarian homogenate is initially rapid but falls to zero within 10 min. Experiments indicate that the inhibition is due to the progesterone formed. Inclusion of RMI 12,936 with the pregn-5-ene-3,20-dione substrate results in a lower final level of progesterone and continuous production of 7α-methyltestosterone. The reduction in the levels of progesterone in presence of RMI 12,936 corresponds closely to the reduction in plasma progesterone in vivo following administration of RMI 12,936 described preivously.
MECHANISM OF ANTIPROGESTATIONAL ACTION OF SYNTHETIC STEROIDS
Authors: Tamaya Teruhiko , Furuta Norio , Motoyama Toshihiko , Boku Sinko , Ohono Yousuke , Okada Hiroji
Published: December 2008

This study was designed to investigate the mechanism of antiprogestational action of synthetic steroids, danazol (17α-hydroxy-pregn-4-en-20-yno [2,3-d] isoxazol-17-ol) and R2323 (13β-ethyl-17α-hydroxy-18,19-dinor-17α-pregna-4,9,11-trien-20-yn-3-one). Oestrogen primed rabbit uteri were used for this study. The sucrose gradient analysis in the supernatant of 248 000 x g (max.) of the uterine homogenate showed that progesterone8S binding was inhibited by each of the synthetic steroid, and the kinetic study revealed that each steroid was a competitive inhibitor, where Kd of progesterone-protein binding was 8.1 × 10−10 m, Ki of danazol-protein binding was 2.7 × 10−8 m and Ki of R2323-protein binding was 6.6 × 10−9m. These results indicate that these synthetic steroids bind to progesterone receptor with moderate binding affinities. The modified Anderson's exchange assay of nuclear receptor demontrated that danazol- or R2323-receptor complex can enter into the uterine nuclei in a lesser degree than does progesterone-receptor complex. RNA synthesis by the uterine chromatin was stimulated if the progesterone-receptor complex was added, but this stimulation was inhibited by addition of danazol or R2323. The chromatin RNA transcription was not induced by danazol- or R2323-receptor complex.

These results suggest that such a synthetic steroid binds to a progesterone receptor, and the steroid-receptor complex enters into the nucleus but does not activate the chromatin template, thus resulting in the antiprogesational effect.
EFFECT OF ENDOCRINE MANIPULATIONS ON GLUCOCORTICOID BINDING CAPACITY IN RAT SKELETAL MUSCLE
Authors: Mayer Michael , Rosen Fred
Published: December 2008

[3H]Dexamethasone binding capacity in rat muscle cytosol was determined after various endocrine manipulations in an attempt to identify factors which might regulate the level of the cytoplasmic hormone receptor protein. Hypophysectomy and adrenalectomy markedly increased the specific binding of [3H]dexamethasone in skeletal muscle cytosol, while implantation of the MtT tumour which secretes ACTH and growth hormone, as well as treatment with glucocorticoids reduced the glucocorticoid specific binding. Since the effects of hypophysectomy and the MtT tumour depend on the presence of the adrenals, they appear to be mediated via changes in circulating glucocorticoid level. Alloxan- or streptozotocin-induced diabetes caused only a slight reduction in the binding of [3H]dexamethasone in muscle, suggesting that the enhanced responsiveness to glucocorticoids in diabetes is not due to increased glucocorticoid receptor activity. There is a sex-dependent effect on binding, female rats having a higher concentration of binding sites. Furthermore, treatment with the synthetic androgen fluoxymesterone or with glucocorticoids reduces binding, while oestradiol-17β enhances it.

The changes in glucocorticoid binding capacity induced by the various endocrine manipulations appear to reflect mainly changes in receptor concentration rather than occupancy, since the binding assays were preformed after a suitable time allowance for removal of the administered hormones by metabolism.
IN VITRO EFFECTS OF THEOPHYLLINE AND AMINOGLUTHETIMIDE UPON BASAL AND ACTH INDUCED cAMP LEVELS AND STEROID OUTPUT BY THE NORMAL HUMAN ADRENAL GLAND
Authors: Honn Kenneth V. , Chavin Walter
Published: December 2008

The in vitro effects of theophylline and aminogluthetimide upon basal and ACTH stimulated cAMP, cortisol and aldosterone responses of normal human adrenocortical tissue were evaluated. Theophylline increased basal cAMP levels and cortisol output, however, basal aldosterone output was depressed. Theophylline in concert with ACTH depressed cortisol and aldosterone output. Aminogluthetimide alone did not affect basal cAMP levels, however, the normal cAMP response to ACTH was delayed in aminogluthetimide pre-treated adrenals. Aminogluthetimide also depressed basal and ACTH stimulated cortisol and aldosterone output with the latter being more sensitive. The findings indicate that both theophylline and aminogluthetimide produce effects upon the adrenal in addition to inhibition of phosphodiesterase and cholesterol side-chain cleavage, respectively. Further, theophylline depression of ACTH stimulated steroid output may be helpful in understanding the interplay between a number of factors in the control of adrenal steroid biosynthesis and release.
CIRCADIAN AND CIRCANNUAL RHYTHMS IN PLASMA HORMONES AND OTHER VARIABLES OF FIVE HEALTHY YOUNG HUMAN MALES
Authors: Reinberg Alain , Lagoguey Michel , Cesselin François , Touitou Yvan , Legrand Jean-Claude , Delassalle Annick , Antreassian Joséphine , Lagoguey Alenka
Published: December 2008

Every other month (plasma) and every month (urine) circadian rhythms were documented during the course of 14 months. Annual changes were validated in the 24 h mean of: plasma FSH (annual crest time: February), LH (March), thyroxine (September), cortisol (February), renin activity (April), testosterone (October), urinary 17-hydroxycorticosteroids (March), aldosterone (March), potassium (May) as well as sexual activity (September) [self-recorded daily]. Plasma prolactin did not show an annual variation. In addition, annual changes in the circadian acrophase (crest time location in the 24 h scale) occurred for some of the documented variables: plasma thyroxine, cortisol, renin activity, testosterone, urinary aldosterone and potassium.
EFFECTS OF CIMETIDINE ON PROLACTIN, LH, AND SEX STEROID SECRETION IN MALE AND FEMALE VOLUNTEERS
Authors: Bohnet H. G. , Greiwe M. , Hanker J. P. , Aragona C. , Schneider H. P. G.
Published: December 2008

The histamine H2-receptor antagonist cimetidine, which has recently been introduced for the treatment of gastric and duodenal ulcers and haemorrhage, respectively, stimulates prolactin (PRL) secretion. The release of PRL after a bolus injection of the compound is significantly higher in female than in male volunteers, and is more pronounced during the luteal than during the follicular phase of the menstrual cycle. Oral administration of the drug stimulates PRL to a similar extent as parenteral administration. Treatment of male and female volunteers with cimetidine for 20 days (1 g/day orally) resulted in elevated serum PRL concentrations in both sexes. Basal LH levels as well as the response to 25 μg LH-RH were not significantly changed after treatment. Testosterone levels in males and oestradiol levels in females were not altered. Luteal progesterone, however, was significantly diminished in the menstrual cycles when cimetidine was given. The mechanism underlying the stimulatory effect of cimetidine on PRL secretion is not clear, but it does not seem that this ability is exerted via an inhibition of pituitary dopamine receptors. The dopaminergic effect of lisuride, an ergot alkaloid, could not be reversed by cimetidine.
PITUITARY-THYROID RESPONSES TO SURGICAL STRESS
Authors: Chan Vivian , Wang Christina , Yeung Rose T. T.
Published: December 2008

The effect of surgery on pituitary-thyroid function was studied in 12 euthyroid patients. There was a sharp early increase in total thyroxine level, causing displacement of triiodothyronine from thyroid hormone binding proteins resulting in the elevation of the biologically more potent free triiodothyronine fraction. The serum triiodothyronine concentration fell rapidly during and after the operation, with a concomitant rise in reverse triiodothyronine level. Increased prolactin levels were found during and after surgery. With no post-operative complication, recovery of normal pituitary-thyroid function occurred after 4 to 7 days of convalescence.
FACTORS AFFECTING THE β-CELL SENSITIVITY TO ALLOXAN IN VIVO
Authors: Boquist L.
Published: December 2008

Blood glucose and pancreatic islet morphology were studied in mice subjected to different kinds of treatment both before and after alloxan administration. d-Glucose, d-mannose, d-fructose, NaHCO3 and sodium lactate protected against alloxan when given before, but not when given after alloxan, whereas l-leucine protected when administered before, and also when injected 1 or 3 min after alloxan. No protection was seen in animals receiving l-leucine 10 min following alloxan. The findings may indicate that the mechanism for alloxan protection by 1-leucine differs from that of the other compounds tested.
LUTEOTROPHIC ACTIVITY OF ECTOPICALLY DEVELOPING RAT BLASTOCYSTS
Authors: Zeilmaker G. H. , Verhamme C. M. P. M.
Published: December 2008

The production of a luteotrophic hormone by ectopically transplanted rat blastocysts was demonstrated by transfer of blastocysts to the kidneys of cyclic and pseudopregnant mice and isogeneic rats.

Pseudopregnancy was induced in nearly all cyclic mice bearing trophoblastic outgrowths but not in cyclic rats. In both mice and rats prolongation of pseudopregnancy was observed following ectopic transplantation of rat blastocysts at the time of normal egg implantation. It is concluded that ectopically developing rat trophoblastic tissue produces a luteotrophic hormone.
TESTICULAR BLOOD FLOW AND TESTOSTERONE CONCENTRATIONS IN THE SPERMATIC VENOUS BLOOD IN RATS WITH EXPERIMENTAL CRYPTORCHIDISM
Authors: Damber Jan-Erik , Bergh Anders , Janson Per Olof
Published: December 2008

Testicular blood flow and testosterone concentrations in the spermatic venous plasma were measured on unilaterally cryptorchid rats. Blood flow to the cryptorchid testis was 31.4 ± 11.7 (sd) ml/100 g x min which was significantly higher than that of the scrotal testis (17.7 ± 4.4 ml/100 gx. min) Stereological analysis showed a relative increase of blood vessel containing interstitial tissue in the cryptorchid testis, which was probably the main factor responsible for the relative increase of blood flow to the cryptorchid testis. The increase of interstitial tissue was greater than the increase of blood vessels and thus, the interstitium in the cryptorchid testis contained a number of vessels which was smaller than that of the interstitium in the scrotally located testis.

The concentration of testosterone in the spermatic vein of the abdominal testis was 18.0 ± 5.5 (sd) ng/ml and the corresponding value for the scrotal testis was 41.2 ± 7.0 ng/ml. Calculations based on functional and morphological data indicate that the function of the Leydig cells in the abdominal testis was impaired. It was concluded that the outflow of testosterone from the cryptorchid testis was highly reduced.
SHORT-TERM REGULATION OF LH AND FSH SECRETION IN CYCLIC WOMEN
Authors: Römmler A. , Baumgarten S. , Schneller E. , Schwartz U. , Hammerstein J.
Published: December 2008

The effects of six consecutive LH-RH injections (25 μg intravenously each) at 90 min intervals on serum gonadotrophin and serum ovarian steroid levels were investigated in cyclic women (n= 13) in the follicular, midcycle and luteal phase of the menstrual cycle.

The maximum response of LH pituitary reaction to repeated LH-RH injections was smallest in the follicular phase, higher in the luteal phase and greatest in the midcycle phase of the menstrual cycle. The maximum response of FSH reaction was small both in the follicular and luteal phase and again greatest in the midcycle phase.

The pituitary response pattern after six consecutive LH-RH injections also varied throughout the cycle. On the one hand there was a constant pronounced increase in the response from the first to the second LH-RH injection for both LH and FSH, while the second of all six increments (Δ2) was the maximum increment. On the other hand, for both LH and FSH the responses Δ3 to Δ6 decreased progressively in the luteal phase and showed an even further pronounced decrease in the midcycle phase, indicating an exhaustion of pituitary secretion. In the follicular phase, however, the decrease in the responses Δ3 to Δ6 for LH was small, but significant. For FSH no significant changes between the responses Δ2 to Δ6 were observed.

Secondary to the elevated gonadotrophin levels, serum levels of oestradiol, 17-hydroxyprogesterone and progesterone increased slightly in the follicular phase and distinctly in the luteal phase of the cycle.

Possible mechanisms are discussed which might provide an explanation for the observed augmentation and subsequent diminution of pituitary reaction.
MALE PROLACTIN SECRETING PITUITARY ADENOMAS IN HUMANS STUDIED BY PEROXIDASE-LABELLED ANTIBODY METHOD
Authors: Osamura R. Yoshiyuki , Watanabe Keiichi , Teramoto Akira , Hirakawa Kimiyoshi , Kawano Nobuyuki , Morii Seiji
Published: December 2008

In order to identity the source of excess secretion of prolactin in male patients, the pituitary tumours of 11 males with hyperprolactinaemia were studied by peroxidase-labelled antibody method using antibodies against human prolactin. Using light microscope, prolactin was demonstrated in most tumour cells in all cases. Ultrastructurally, prolactin was localized mainly on the secretory granules. Immunohistochemically positive cells were thought to correlate wih first type of tumour cells which were the major component observed by regular electron microscopic study without immunohistochemical staining. These findings indicated the secretion of excess amount of prolactin by the tumour cells and were considered to be responsible for the category of Male Prolactin Secreting Pituitary Adenoma. The mechanism by which these male hyperprolactinaemic patients are endocrinologically non-functioning is also discussed.
GONADOTROPHIN REGULATION IN THE LACTATING RAT
Authors: Steger R. W. , Peluso J. J.
Published: December 2008

Post-partum lactation in the rat is associated with follicular quiescence and an attenuation of gonadotrophin secretion. The present study demonstrates that the lactating rat responds to exogenous LH-releasing hormone (LH-RH) in a manner similar to dioestrous rats. Oestrogen priming increases the LH and FSH response to LH-RH to a smaller degree in ovariectomized, lactating, than in non-lactating, ovariectomized rats. Pituitary LH levels throughout lactation did not seem to be related to LH-RH-induced LH release. A diminished post-castration rise in both LH and FSH, and a diminished positive feedback response to oestrogen administration were also observed and may indicate a disruption of gonadotrophin regulation at both the hypothalamic and the pituitary level.
PLASMA LEVELS OF GROWTH HORMONE IN FEMALE RATS OF DIFFERENT AGES
Authors: Edén Staffan , Albertsson-Wikland Kerstin , Isaksson Olle
Published: December 2008

Radioimmunoassayable growth hormone (GH) was determined in fed and fasted female rats of different ages. In 6–40 day-old rats blood was collected at hourly intervals in groups of rats at different time intervals during the day. Within each age group the variation in plasma GH was considerable. In 6–14 day-old rats plasma GH was generally elevated. By day 18 levels declined, lowest on day 22 and by day 26 again increasing. In 14 day-old rats the median plasma level of GH was 22 ng/ml, in 22 day-old rats < 5 ng/ml and in 40 day-old rats 43 ng/ml. In 14 day-old rats levels ranged from < 5 ng/ml – 148 ng/ml, in 22 day-old rats from < 5 ng/ml – 34 ng/ml and in 40 day-old rats from < 5 ng/ml – > 200 ng/ml. A 20 h fasting period was associated with a significant decrease in plasma GH. In 45 day-old rats, the variations in plasma GH of individual animals were studied by obtaining sequential blood samples from unrestrained, undisturbed animals with implanted intra-aortic cannulae. In these rats GH secretion was characterized by an episodic release, occurring every 2–4 h. After a 20 h fasting period major peaks were depressed and occurred less frequently. It is concluded that there is an age-related as well as a circadian rhythm in growth hormone secretion in the rat and that sequential sampling of blood is essential for the evaluation of the secretory pattern.
CHANGES OF THE HYPOTHALAMUS-PITUITARY-THYROID AXIS IN STREPTOZOTOCIN-DIABETIC RATS DURING ADAPTATION TO A LOW IODINE DIET
Authors: Montoya Eladio , González Concepción , Lamas Luis , Jolín Trinidad , González Margarita
Published: December 2008

Studies on the hypothalamus-pituitary-thyroid axis have been carried out in control and in diabetic male Wistar rats during adaptation to a 125I-labelled low iodine diet. Diabetes was induced by a single streptozotocin injection (7 mg/100 g body weight). Thyroid weight, thyroid 127I and 125I content, [125I]iodoamino acid distribution in thyroid digests, plasma PBI, plasma and pituitary TSH and hypothalamic TRH by radioimmunoassay were measured between 5 and 30 days after saline or streptozotocin injection, corresponding to 15 and 40 days after onset of the 125I-LID. As compared to controls, diabetic animals have smaller thyroids. The 125I and 127I in diabetic thyroids between 5 and 10 days was lower than in control glands; at longer intervals both 125I and 127I increased with time in diabetics, while no remarkable changes were seen in the control glands. Furthermore, the percentage of T3 and the MIT/DIT and T3/T4 ratios in thyroids of diabetic were lower than in the corresponding control group at all intervals. These results are compatible with a deficiency of TSH stimulation and/or with a high thyroidal iodine content.

Compared to the controls, each group of diabetic rats presented a significantly lower plasma TSH concentration, in spite of the fact that its plasma PBI is more or similarly reduced in diabetic than in controls. Furthermore, the decreased pituitary TSH secretion in diabetic rats at early intervals is lower than in controls although the pituitary TSH and hypothalamic TRH remain within normal ranges. It is concluded that the decrease in pituitary TSH secretion may be the result of a reduction of pituitary TRH stimulation, secondary to a diminished secretion and/or synthesis of TRH by the hypothalamus.
IN VITRO EFFECT OF 16α-HYDROXYPROGESTERONE ON THE ENZYME ACTIVITIES RELATED TO ANDROGEN PRODUCTION IN HUMAN TESTES
Authors: Inano Hiroshi , Tamaoki Bun-ichi
Published: December 2008

Progesterone was converted in vitro to 16α- and 17α-hydroxyprogesterones in the presence of NADPH by the testicular microsomal fraction (precipitate at 10 000 × g−105 000 × g) obtained from patients with prostatic carcinoma. 16α-Hydroxyprogesterone was not metabolized by either the microsomal or the cytosol fractions, and accumulated in the incubation medium. 16α-Hydroxyprogesterone competitively inhibited the activity of the C-17−C-20 lyase in the testicular microsomal fraction with an estimated inhibitor constant of 72 μm. Moreover, the 16α-hydroxyprogesterone non-competitively inhibited the activity of the 20α-hydroxysteroid dehydrogenase in the testicular cytosol fraction and had an estimated inhibitor constant of 52.9 μm. Other testicular enzymes related to steroid metabolism, such as Δ5-3β-hydroxysteroid dehydrogenase coupled with the Δ4-Δ5 isomerase, 16α-hydroxylase, 17α-hydroxylase and 17β-hydroxysteroid dehydrogenase were not influenced in vitro by 16α-hydroxyprogesterone at the concentration of 0.1 mm. From these findings, it is concluded that 16α-hydroxyprogesterone inhibit specifically the cleavage of the side-chain of 17α-hydroxypregnenes in the course of androgen formation from pregnenolone in vitro.
DISSOCIATION OF PLASMA AND CSF PROLACTIN HETEROGENEITY
Authors: Jordan Richard M. , Kendall John W.
Published: December 2008

Plasma and cerebrospinal fluid (CSF) specimens from 3 patients with suprasellar extension of a pituitary tumour were fractionated by column chromatography. "Big" and "little" prolactin were found in plasma but only "little" prolactin was found in CSF. Prolactin containing CSF from 2 of the patients was incubated with prolactin-free plasma and chromatographed. The elution patterns demonstrated a striking shift toward the [1251] albumin marker resembling the "big" and "little" prolactin pattern seen in native plasma. In addition, [125I]h prolactin was incubated with prolactin-free plasma and rechromatographed. A substantial early eluting peak of radioactivity occurred in the zone of albumin elution. The presence of only "little" prolactin in CSF and the conversion of CSF "little" prolactin to "big" prolactin by exposure to plasma suggest that "big" prolactin is not a prohormone but results from binding of "little" prolactin to plasma proteins or aggregation of "little" prolactin in the presence of plasma.
THE INFLUENCE OF CHRONIC RENAL FAILURE ON SERUM AND URINARY THYROID HORMONE LEVELS
Authors: Kølendorf Klaus , Møller Birger Broch , Rogowski Preben
Published: December 2008

The effects of various degrees of chronic renal failure on serum and urinary thyroid hormones were studied in 10 patients with a mean creatinine clearance (Cr.Cl.) of 23 ml/min (group A), in 11 patients with a Cr.Cl. of 5.7 ml/min (group B), and in 60 healthy euthyroid subjects with normal renal function. We found a significant decrease (P < 0.01) of serum total thyroxine (T4) (5.3 ±1.9 (sd) μg/100 ml in group A and 4.1 ± 1.5 in group B), serum total triiodothyronine (T3) (65.4 ± 17.4 ng/100 ml ~57.4 ± 13.9), serum free T4 (5.60 ± 1.74 arb.U ∼ 4.45 ± 1.61), and serum free T3 (69.51 ± 21.22 arb.U ∼ 62.09 ± 12.39). T3 uptake test and basal thyroid stimulating hormone (TSH) values were normal in both groups of renal patients.

No statistical significance was found in T4 excretion in urine. Urinary T3 excretion was significantly reduced (P < 0.01) in group A (27 ± 44 ng/24 h), and undetectable in terminal renal failure. Urinary protein excretion was non-selective and low (median 0.2 g/24 h and 0.7 g/24 h, respectively).

Conclusively we have found reduced levels of serum total and free T3, and in contradiction to most investigators substantially reduced levels of serum total and free T4. Urinary excretion of T4 and T3 reflects the low levels of free serum hormones and the tubular impairment.
NEUROTRANSMITTER CONTROL OF THYROTROPHIN SECRETION IN HYPOTHYROID RATS
Authors: Männistö P. T. , Ranta T.
Published: December 2008

The effect of drugs modifying dopaminergic, noradrenergic and serotonergic systems on the serum TSH levels was studied in the male rats made hypothyroid by giving 10 mg/l of propylthiouracil in tap water for 4 days. Apomorphine (2.5 mg/kg, given once −30 min before sacrifice; or four times −120, 90, 60 and 30 min before sacrifice), bromocryptine (10 and 20 mg/kg, 2 h before sacrifice) and piribedil (50 and 100 mg/kg, 4 h) decreased the serum TSH concentrations. The effect of a single dose of apomorphine (2.5 mg/kg, 30 min before sacrifice) was partially reversed by a pimozide pre-treatment (2.5 mg/kg, 2 h). Clonidine (1 mg/kg but not 0.01 or 0.1 mg/kg, 2 h before sacrifice) further elevated the high TSH levels whereas α-methyl-p-tyrosine (300 mg/kg, 2 h), phenoxybenzamine (50 mg/kg, 2 h) and diethyldithiocarbamate (300 mg/kg, 2 h) significantly decreased TSH secretion. The effect of clonidine (1 mg/kg, 2 h) was partially antagonized by phenoxybenzamine (20 mg/kg, 2 h). A high dose of 5-HTP (300 mg/kg, 2 h) increased serum TSH concentrations whereas p-chlorophenylalanine (100 mg/kg, 2 h) decreased it. When both drugs were given together, the serum TSH levels did not change. L-tryptophan (100–300 mg/kg, 2 h) uniformly decreased the serum TSH concentrations in all experiments. It is concluded that in the hypothyroid rats, the secretion of TSH is inhibited by dopaminergic system, and stimulated by noradrenergic system. The effect of 5-HT pathways remained an open question.
ROLE OF ANGIOTENSIN III IN THE REGULATION OF BLOOD PRESSURE, PLASMA ALDOSTERONE AND PLASMA RENIN ACTIVITY IN RABBIT
Authors: Saito Ikuo , Saruta Takao , Eguchi Toyohisa , Kondo Kazuoki , Nakamura Ryuichi , Matsuki Shun
Published: December 2008

To evaluate the role of angiotensin III in the control of blood pressure, plasma aldosterone and plasma renin activity (PRA), the pressor, steroidogenic and PRA-suppressing effect of angiotensin III was studied in rabbits with or without simultaneous constant infusion of Ile7-angiotensin III, an analogue of angiotensin III, or Sar1Ala8-angiotensin II, an analogue of angiotensin II, and compared with the effect of angiotensin II.

Infusion of 30 ng/kg/min of angiotensin III or angiotensin II produced a twofold increase in plasma aldosterone. Pressor response to angiotensin III was approximately one tenth of that of angiotensin II. Infusion of angiotensin II suppressed the PRA significantly, while infusion of angiotensin III did not suppress it. Angiotensin II or angiotensin III induced-increase in plasma aldosterone was attenuated by the pretreatment with either Ile7-angiotensin III or Sar1Ala8-angiotensin II. Pressor or PRA-suppressing action of angiotensin II was unaffected by the pre-treatment with Ile7-angiotensin III, while it was significantly inhibited by pre-treatment with Sar1Ala8-angiotensin II.

This study indicates that angiotensin III or angiotensin III analogues affect the adrenal glands selectively and suggests that there are differences between the receptor sites for angiotensins in vascular smooth muscle, kidney and those in the adrenal cortex.
STUDIES OF SEXUAL DIFFERENTIATION OF SHEEP
Authors: Wilson P. R. , Tarttelin M. F.
Published: December 2008

Forty ewes were given intramuscular injections of testosterone cypionate (200 mg) on each of the 20th, 27th and 40th days of gestation. This treatment ensured foetal exposure to testosterone from day 20 to day 65. Forty untreated ewes acted as controls. At birth, pre-natally androgenised male lambs were anatomically normal, but similarly treated female offspring displayed complete external genital masculinisation including the presence of a prepuce, penis and scrotum and the absence of an external vulval opening. No male gonads were present. Internally, the female lambs possessed ovaries, uteri, cervices and vagina of normal appearance. Two-weekly blood plasma samples were withdrawn from 10 androgenised and 6 control female offspring and 8 androgenised and 8 control male offspring from 4–30 weeks of age. Testosterone levels in males and LH levels in males and females were measured by radioimmunoassays. Analyses of variance showed that post-natal plasma LH levels in pre-natally androgenised lambs (male and female) were significantly depressed (P < 0.001), and that plasma testosterone concentrations in pre-natally androgenised males were subsequently depressed (P < 0.001). These results suggested that pre-natal androgenisation impaired hypothalamic hypophysiotrophic and/or pituitary function during the first 30 weeks of post-natal life which resulted either directly, or indirectly via reduced LH output, in a suppression of testosterone production by the testes.
CLINICAL STUDIES OF "BIG ACTH": ITS PHYSICO-CHEMICAL CHARACTERISTICS
Authors: Yamada Yukio , Ito Seiki , Miyashita Masahiro , Kaneko Kenzo , Watanabe Toru , Shibata Akira , Sasaki Hideo , Tsutsui Kazuya , Kayamori Ryo
Published: December 2008

The big ACTH fractions available from human plasma and pituitary glands and from porcine pituitary glands were physico-chemically characterized by gel filtration, disc electrophoresis and isoelectric separation.

In the case of healthy human subjects, big ACTH fractions were isolated by gel filtration from plasma samples taken during states of acute ACTH hypersecretion such as the lysine-8-vasopressin, insulin or metopyrone tests though none of these fractions were isolated from plasma sampled under normal conditions. Even with no stimulation of ACTH secretion, patients with Cushing's disease gave plasma samples that contained an isolable big ACTH fraction, but such a fraction was hardly isolated from plasma taken from patient with Addison's disease. Both human pituitaries and porcine pituitaries contained an isolable big ACTH fraction. By a gel filtration analysis the molecular weight of the big ACTH was estimated to be higher than 20 000. Disc electrophoresis with an acrylamide gel indicated that big ACTH is strongly basic while small ACTH is more acidic than pH 8.3. Isoelectric separation revealed that the isoelectric point of human big ACTH is higher than pH 10.0 while that of small ACTH is about pH 6.8.
DIFFERENT BEHAVIOUR OF 19S THYROGLOBULIN EXTRACTED FROM NORMAL THYROID, SIMPLE GOITRE AND TOXIC GOITRE IN POLYACRYLAMIDE SLAB GEL ISOELECTRIC FOCUSING
Authors: Massi G. , Crivelli F.
Published: December 2008

19S thyroglobulin (19S TG) was isolated from normal thyroids, simple goitres and one case of toxic goitre (Graves' disease). With isoelectric focusing on polyacrylamide gel slabs (pH 4–6) several bands for each specimen were detected.

The migration patterns of the toxic goitre 19S TG were clearly different from the patterns of normal 19S TG and simple goitre 19S TG.
ACTION OF KI AND SEVERAL IODOCOMPOUNDS ON [3H]URIDINE INCORPORATION INTO THYROID RNA
Authors: de Pisarev D. L. Kleiman , Pisarev M. A. , Juvenal G. J.
Published: December 2008

The present studies were performed in order to further clarify the action of iodine and iodocompounds on the incorporation of labelled uridine into thyroid RNA. KI decreased RNA labelling but did not alter total [3H] uridine uptake or [3H]inulin distribution space. KI also inhibited the increase in RNA labelling produced by 8 mm glucose. T4 was more potent on a molar basis than KI in impairing uridine incorporation. TETRAC, TRIAC and isopropyl-T3 also decreased RNA labelling, while T2 and isopropyl-T2 were ineffective.

KI did not alter the distribution of the uridine derivatives, UMP, UDP and UTP, as determined by the distribution of [3H] uridine in these compounds by paper chromatography, suggesting that the action of KI does not take place at the step of uridine phosphorylation. Like its effect on TSH, KI also impairs the stimulatory effect of exogenous cAMP and cGMP on RNA labelling, suggesting that its action is exerted beyond the step of cyclic nucleotide formation.

Iodine and iodocompounds may exert their inhibitory action on RNA labelling at the step of nucleotide polymerization.
THE HORMONAL REGULATION OF HEPATIC MICROSOMAL 11β-HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN THE RAT
Authors: Lax Edmund Rodney , Ghraf Rüdiger , Schriefers Herbert
Published: December 2008

Hepatic microsomal 11β-hydroxysteroid dehydrogenase activity is higher in male than in female rat liver. Gonadectomy on day 25 of life only affects the activity in the adult male animal, causing a decrease towards the normal female level. Administration of testosterone to gonadectomized rats of either sex causes the induction of typical male activity levels. On the basis of these experiments, this enzyme activity may be classified as androgen-dependent. However, 11β-hydroxysteroid dehydrogenase differs from other known androgen-dependent activities in that administration of oestradiol to gonadectomized animals of either sex causes a further significant repression of the activity to levels close to the limits of detection. Hypophysectomy on day 50 of life does not affect the activity in 75 day-old male rats, but causes the appearance of typically male activity levels in females. These results indicate that the hypophysis exerts a repressive influence on hepatic 11β-hydroxysteroid dehydrogenase in female rats. The fact that this activity is not influenced by androgen or oestrogen administration once the pituitary has been removed demonstrates the obligatory role of the hypophysis for sex hormone action.
THE DISTRIBUTION OF HORMONE-SENSITIVE ADENYLATE CYCLASE IN RAT KIDNEY AND THE INTERACTION OF HORMONES IN ACTIVATING THE ENZYME
Authors: Nagata Naokazu , Araki-Shimada Nobuko , Ono Yuriko , Kimura Narimichi
Published: December 2008

The effects of parathyroid hormone (PTH) and calcitonin (CT) on cAMP metabolism in rat kidney were examined with particular attention to the localization of the hormone-sensitive adenylate cyclase. In the cortical slices, CT produced an accumulation of cAMP only in the absence of PTH or in the presence of PTH in concentrations which did not induce a maximal increase in the cAMP levels. The lack of additive effect of PTH and CT was confirmed by examining the production of [14C]cAMP in the pre-labelled tissue. Although PTH-sensitive adenylate cyclase was demonstrated predominantly in the renal cortex, PTH also stimulated the enzyme of the tip of the renal papilla. The effect was elicited even in the presence of maximally effective concentrations of vasopressin (ADH). CT-sensitive adenylate cyclase was distributed through all the regions of the kidney except for the papillary tip. Its pattern of distribution exhibited a biphasic curve with peaks at inner medulla and outer cortex. The effect of CT on the enzyme from the papillary base was detected only in the absence of ADH. Additivity of the combined stimulation by addition of PTH and CT on adenylate cyclase varied in different regions of the kidney. Additivity was apparently total in papilla, but partial in medulla and absent in cortex. It is concluded that, although the patterns of distribution of adenylate cyclase responsive to PTH, CT and ADH are different, there are interactions of different degrees among the hormones in stimulating renal adenylate cyclase. This is especially true in the renal cortex, where the majority of PTH or CT sensitive adenylate cyclase activity are present. It seems that all the CT-responsive system is partly involved in the system responsive to PTH.
THE ROLE OF THE HYPOTHALAMUS IN THE TONIC SECRETION OF PROLACTIN INDUCED BY OESTROGENS IN THE RAT
Authors: Kato H. , Velasco M. E. , Rothchild I.
Published: December 2008

To investigate where oestrogens act to induce an increase in the tonic release of prolactin, the effect of ovariectomy alone or of ovariectomy plus oestradiol benzoate treatment (10 μg/day for 7 days) (OeB10) on the morning prolactin serum level in adult female rats was determined after each of the following procedures: frontal hypothalamic deafferentation (FHD) (a semi-lunar cut at the caudal border of the optic chiasma, separating the anterior hypothalamus from the preoptic area); medial hypothalamic deafferentation (MHD) (a similar cut, but separating the anterior from the posterior half of the hypothalamus); sham deafferentation; an electrolytic lesion of the arcuate-median eminence area (Arcuate-ME lesion); hypophysectomy and pituitary autotransplantation beneath the kidney capsule. The rats were ovariectomized 1 week after the latter procedure, or 3 weeks after the others, and OeB10 or oil vehicle treatment was begun one week after ovariectomy.

FHD, the Arcuate-ME lesion and pituitary autotransplantation markedly increased the basal prolactin level; MHD induced a much smaller increase. The level fell after ovariectomy only in the FHD group. A sharp and equal increase in the prolactin level occurred in the FHD, MHD and sham operation groups in response to OeB10; a much smaller and more variable increase occurred in the Arcuate-ME and pituitary autotransplantation groups.

The results suggest that oestrogens increase the tonic release of prolactin only in part by a direct action on the pituitary, and more importantly by acting on the posterior half of the hypothalamus or on areas with lateral, superior, or posterior afferent connections to this site.
CIRCADIAN AND 30 MINUTES VARIATIONS IN SERUM TSH AND THYROID HORMONES IN NORMAL SUBJECTS
Authors: Weeke Jørgen , Gundersen Hans Jørgen G.
Published: December 2008

Ten normal young males were investigated in order to examine diurnal and short-term variations in serum TSH and serum thyroid hormones. In five subjects blood samples were obtained every 30 min during a 24 h period of daily life. A synchronous diurnal rhythm was found for free T3 and serum TSH with low levels in the day-time and higher levels at night. The mean increase from day to night was 15 and 140 per cent, respectively. There was a tendency to a similar rhythm in free T4, but the increase of 7 per cent fell short of statistical significance. In the other five men blood samples were obtained every 5 min in a 6 to 7 h period starting within the interval from 19.15 to 22.00 h. A significant regular variation with a cycle-length of half an hour was found in TSH, free T3 and free T4. This rhythm accounted for a significant part of the total variation in the levels of TSH, free T3 and free T4. The mean amplitude of the short-term variation is 13, 15 and 11 per cent of the mean level of the respective hormones. The data suggest a pulsatile release of hormones from the thyroid gland governed by a pulsatile TSH secretion.
CORRELATION OF REVERSE-T3 AND 3,3′-T2 (T2′) PLASMA CONCENTRATIONS UNDER PHYSIOLOGICAL AND EXPERIMENTAL CONDITIONS IN MAN
Authors: Hüfner M. , Grussendorf M.
Published: December 2008

T2′ plasma levels are measured under different conditions and correlated to the respective rT3 concentrations. Specific RIAs for T2′ and rT3 are used. Pharmacological doses of T3 cause an increase of plasma T2′; if T3 or T4 doses are administered to an athyroid patient which cause a similar level of plasma T3 the increase of T2′ is much larger during T4 treatment. Cord blood levels of T2′ are 2–3-fold higher than in normal adults whereas rT3 concentrations are about 10 times higher than normal. After birth rT3 and T2′ levels decrease in about a parallel manner. After a bolus iv injection of 500 μg rT3, T2′ starts to increase as early as 2 min after injection.

PTU in therapeutic doses causes a rapid increase of plasma rT3 with a maximum 4 h after ingestion. A dose of 150 mg PTU causes a maximum of about 100% above baseline. T2′ also increases but to a lesser degree (about 50 % above baseline).

We conclude that rT3 is the most important precursor of T2′ whereas T3 contributes only to a minor degree to the total T2′ production under physiological conditions.
THE EFFECT OF LITHIUM ON THE PERIPHERAL TURNOVER OF THYROXINE AND TRIIODOTHYRONINE
Authors: Kvetny Jan
Published: December 2008

The effect of lithium on the peripheral turnover of T4 and T3 was investigated in 14 euthyroid subjects using lymphocytes as target cells. Lithium caused a dose-dependent rise in T4 turnover, which did not lead to increased T3 production, but no rise in T3 turnover. A further 3 patients with lithium induced hypothyroidism were studied. Patients with high T4 turnover had high TSH values and in these patients lithium induced a decrease in T4 turnover.

This may lead to the conclusion that the demonstrated effect of lithium in the control group did not cause the low T4 in these patients. In 2 patients defective T4 degradation was demonstrated.
UNCONJUGATED OESTETROL IN PLASMA IN RESPONSE TO AN INTRAVENOUS LOAD OF DEHYDROEPIANDROSTERONE SULPHATE (DHAS) IN UNCOMPLICATED AND COMPLICATED HUMAN PREGNANCY
Authors: Axelsson Ove
Published: December 2008

A non-chromatographic radioimmunoassay for estimation of unconjugated oestetrol in plasma from pregnant women is described. The antiserum has a high specificity to oestetrol. The technical procedure is simple and rapid. Only small amounts of plasma (0.2–0.4 ml) are needed for the analysis. The method has been applied to the measurement of oestetrol in plasma from pregnant women before and after an intravenous injection of 50 mg DHAS. In women with uncomplicated pregnancies a rise of plasma oestetrol was found 60 min after the injection. From 120 to 360 min there was a plateau level, at 600 min a decrease from this level was observed. No changes in the oestetrol response were found with advancing gestational age from the 33rd to the 40th week of pregnancy. A great spread in the individual responses were recorded. Patients with pre-eclampsia and intrauterine growth retardation had a tendency to a lower increase and patients with diabetes a tendency to a higher increase of plasma oestetrol after the DHAS administration. From the data obtained it is concluded that the increase of plasma oestetrol after an intravenous injection of DHAS in most cases is secondary to the increase of plasma oestradiol. The results suggest that measurement of unconjugated oestetrol in plasma after an intravenous load of DHAS is no safe way to assess foetal wellbeing. In women with intrauterine growth retardation (IUGR) the simultaneous measurement of plasma oestradiol and oestetrol after an injection of DHAS indicates a possibility to distinguish placental from foetal causes of this syndrome.
A QUANTITATIVE STUDY ON FEEDBACK CONTROL OF LH BY TESTOSTERONE IN YOUNG ADULT AND OLD MALE RATS
Authors: Pirke Karl M. , Geiss Michael , Sintermann Rainer
Published: December 2008

The hypothalamic-pituitary gonadal axis was studied in young adult (3 month old) and old (24 to 27 month old) male Wistar rats. Plasma testosterone decreased significantly in old animals (x̄: 262 ng/100 ml (n = 35); versus x̄: 110 ng/100 ml (n = 30)). The fall in LH was less pronounced but still significant (54.5 ng LH-RP-1/ml in young versus 39.5 ng/ml in old rats). Groups of 6 to 8 animals of both ages were castrated and implanted with silastic capsules continuously releasing testosterone. The length of the capsules was directly proportional to the plasma testosterone levels achieved (range between 63 and 350 ng/100 ml).

After one week young castrated rats not substituted with testosterone showed LH values three times higher (x̄: 351 ng/ml) than old rats treated in the same way (x̄ = 126 ng/ml). LH values in the animals substituted with testosterone indicate that the sensitivity of the negative testosterone-LH feedback is greatly increased in old rats. Testosterone can be depressed to 60 ng/100 ml before an increase in LH occurs. In young rats no increase in LH was observed when testosterone values were higher than 170 ng/100 ml. In the range between 170 and 100 ng/100 ml about half of the young animals reacted with increased LH secretion, while an increase was observed in all young animals when testosterone dropped below 100 ng/100 ml.
BASAL AND TRH-STIMULATED THYROID AND PITUITARY HORMONES IN VARIOUS DEGREES OF RENAL INSUFFICIENCY
Authors: Weissel M. , Stummvoll H. K. , Kolbe H. , Höfer R.
Published: December 2008

Abnormalities of thyroid and pituitary function are well recognized in patients with end-stage renal failure. We have investigated the influence of varying degrees of renal insufficiency on serum thyroid (total thyroxine, TT4; total 3,5,3′-triiodothyronine, TT3, and 3′,5′,3′-triiodothyronine, reverse T3) and pituitary (thyrotrophin, TSH; growth hormone, GH; prolactin, PRL) hormone levels before and after 200 μg thyrotrophin releasing hormone (TRH) iv administration.

Patients with mild renal insufficiency (= group 1, plasma creatinine (Cr) > 1.3 mg% but < 3.0 mg%) had normal basal and TRH-stimulated hormone concentrations. In patients at a more advanced stage of the disease (= group 2; Cr > 3.0 mg % but < 7.0 mg %) basal hormone concentrations were also normal. In contrast to the normal group, where no GH reaction to TRH could be detected, GH serum concentrations increased in these patients after TRH. The TT3 and PRL response to TRH remained normal. The TSH reaction to TRH was blunted in four, normal in two and exaggerated in one patient. Patients with end-stage renal failure (= group 3; Cr > 7.0 mg%) had significantly decreased basal TT3 concentrations but a normal TT3 response to TRH. Basal TT4, TT3 and TSH concentrations were normal. The TSH reaction was blunted in four and normal in three patients. The mean basal GH was elevated, albeit not significantly different from the control mean value. The GH increase after TRH was even more pronounced than in group 2. Basal PRL concentrations were significantly increased, but maximal differences between basal and TRH-stimulated concentrations were not significantly different from control.

Our data suggest that changes in the pituitary and hypothalamic control of GH are an early consequence of renal insufficiency. Alterations in thyroid function occur simultaneously on the pituitary – hypothalamic and peripheral level at a more advanced stage of the disease. PRL basal levels increase with decreasing renal function. In contrast to other studies we could not observe any significant influence of uraemia on the TRH-stimulated PRL reserve of the pituitary.
QUANTITATIVE AND FUNCTIONAL ASSESSMENT OF PERIPHERAL T-LYMPHOCYTES IN THYROID DISEASES
Authors: Grinblat Joseph , Shohat Batya , Lewitus Zigmund , Joshua Henry
Published: December 2008

A functional as well as quantitative assessment of the peripheral T-lymphocytes was made in 90 patients with various forms of thyroid diseases, 43 with Graves' disease (GD), 23 with non-toxic multinodular goitre (NTMG), 18 with toxic nodular goitre (TNG) and 12 with well-differentiated thyroid cancer (TC), using the E rosette-forming test and the local graft-versus-host reaction (GVHR). Forty healthy volunteers served as controls. In addition, the glands removed from the 38 patients who underwent operation were evaluated histologically for lymphocytic infiltration. The percentage of E rosette-forming cells was found to be significantly lower than normal (58.0 ± 9.03) in the patients with GD (48.7 ± 9.83, P <0.01), NTMG (47.61 ± 12.34, P< 0.01) and TNG (48.8 ± 11.1, P < 0.02). The absolute T-cell count was significantly lower than normal (1207 ± 443) in the patients with GD (973 ± 331, P < 0.05) and NTMG (890 ± 360, P <0.02). The GVHR was completely negative or weakly positive in only 2 of the 40 (5 %) controls, in 14 of the 39 (35.9 %) patients with GD, 14 of the 23 (60.8 %) with NTMG, 9 of the 17 (53 %) with TNG and 3 of the 12 (25 %) with TC. The amount of lymphocytic infiltration in the surgical specimen showed no correlation with the T-cell count and GVHR of the peripheral blood lymphocytes of the patients. Analysis of the data in the group as a whole also failed to reveal any correlation between the GVHR and E rosette test. The GVHR is a functional test while the E rosette is a quantitative test. The findings of this study indicate that there is an impairment in the functional activity of the T-lymphocytes, patients with nodular goitre having shown a more pronounced impairment of cell-mediated immunity than those with GD and TC.