bluuebunny/crossref_metadata_2025 huggingface dataset:
CORRELATION BETWEEN SOMATOMEDIN A IN SERUM AND BODY HEIGHT DEVELOPMENT IN HEALTHY CHILDREN AND CHILDREN WITH CERTAIN GROWTH DISTURBANCES
Authors: Hall Kerstin , Filipsson Rune
Published: December 2008

The somatomedin A level in serum was determined in a series of 66 children in whom longitudinal data on body height growth and dental development were available. The series comprised normal children as well as children with some different types of growth disturbances. A high correlation was found between the somatomedin A level and the age at a certain stage of the dental maturity (r = −0.67) and between the somatomedin A level and the growth rate at this age (r = 0.67). The different groups of patients ranging from pituitary dwarfs to unusually tall children demonstrated a continuous gradient in the correlation between the level of somatomedin A and the different variables of the somatic development.
EFFECTS OF GENERAL ANAESTHESIA AND SEVERITY OF SURGICAL STRESS ON SERUM LH AND TESTOSTERONE IN MALES
Authors: Nakashima A. , Koshiyama K. , Uozumi T. , Monden Y. , Hamanaka Y. , Kurachi K. , Aono T. , Mizutani S. , Matsumoto K.
Published: December 2008

Significantly decreased levels of serum testosterone from the pre-anaesthesia level were found during and up to 7 days following major surgery under general anaesthesia (nitrous oxide, oxygen and halothane following induction with thiopental and succinylcholine chloride) in 18 male patients. On the other hand, in the same patients, the serum luteinizing hormone (LH) increased significantly from the pre-anaesthesia level 30 min and 1 h after the beginning of anaesthesia. A slight increase in LH level was also noted on the 7th post-operative day. The determinations of serum testosterone and LH in fiberoptic bronchoscopy under the same general anaesthesia as that used in surgery or local anaesthesia in 26 male patients, revealed that the change in the serum LH during and following surgery seemed to be mainly induced by the general anaesthesia and that the rate of decrease in the serum testosterone may be related to the severity of surgical stress including the anaesthesia.

The rate of increase in serum testosterone following the injection of gonadotrophin in 20 males on the 6th post-operative day was similar to that in 10 pre-operative males. The effects of pulmonary lobectomy on serum testosterone and urinary steroids were also studied in 6 males under adrenal suppression with dexamethasone. On the 6th post-operative day, the urinary aetiocholanolone plus androsterone and serum testosterone were found to be half the level of those on the pre-operative day, while the urinary 5β-pregnane-3α,17α,20α-triol remained unchanged. These observations in human are not inconsistent with the report of Tcholakian & Eik-Nes (1971) in dogs namely that a shift in androgen biosynthetic pathway is present in the testis under surgical stress.
THE EXCHANGE OF THYROXINE BETWEEN PLASMA AND LIVER: THE ROLE OF FREE THYROXINE
Authors: Hillier A. P.
Published: December 2008

An investigation has been made into the exchange of thyroxine between human plasma and the perfused rat liver. A stop-flow method was used to hold plasma within the liver sinusoids for periods up to 20 MIN. At 20°C it was found that thyroxine present in the sinusoids transferred to the liver at a rate of 5–6%/min; and that thyroxine transferred from the liver to the plasma at a rate of 1 %/min. In a second series of experiments, trace amounts of free thyroxine were injected into the stream of plasma just as it entered the tissue; the liver captured 18.5% of this injected hormone.

In the Discussion it is noted that 29 % of the plasma thyroxine dissociates into free solution each minute. If the liver is able to capture 18.5% of this hormone (as the above experiment suggests) then the plasma-to-liver transfer rate would be 5–6 %/min, which is the rate actually observed. These observations strongly suggest that the transfer of thyroxine from plasma to liver involves its initial release into the free state followed by trapping by the tissue binding sites.
THE POSTNATAL OCCURRENCE OF BIOGENIC MONOAMINES IN PANCREATIC ISLETS OF GOLDEN HAMSTERS
Authors: Cegrell Lennart
Published: December 2008

Fluorescence histochemical studies in newborn and young golden hamster have revealed that some cells in the islets of Langerhans contain monoamine. These cells can be seen in newborns and up to ten day old animals, at least in three to five days old animals the amine behaves like dopamine and is mostly stored in the A2-cells.
ON THE MODULATING EFFECTS OF OVARIES ON NEONATAL ANDROGEN PROGRAMMING OF RAT LIVER ENZYMES
Authors: Stenberg Åke
Published: December 2008

The metabolism of 4-[4-14C]androstene-3,17-dione in rat liver microsomal and cytosol fractions was investigated in adult female rats treated with 1.45 μmole of testosterone propionate at birth. The effects of ovariectomy at 14 and 43 days of age on neonatal testosterone imprinting of enzyme levels were studied. Animals spayed 14 days after birth showed a typical masculinized hepatic enzyme activity pattern with a decreased level of the 5α-reductase activity and increased levels of 5α-reductase, 16α-hydroxylase and 17α- and 3β-hydroxysteroid reductase levels. The pattern was essentially the same in testosterone propionate-treated rats spayed 43 days after birth – with the exception of a feminized 5α-reductase activity – whereas a completely feminized ("de-imprinted") pattern of enzyme activities was found in the rats with intact ovaries at the time of death. It is concluded that de-imprinting action of ovaries is mainly of a reversible nature.
HORMONE AND ENZYME ASSAYS IN PREGNANCY
Authors: Christensen Arne , Hagelid P. E.
Published: December 2008

A rapid and simple method for determination of the placental cystineaminopeptidase (P-CAP) activity in plasma is presented. The enzymecatalysed hydrolysis of the substrate, l-cystine-bis-p-nitroanilide, is followed in a spectrophotometer by reading the absorbance of the product p-nitroaniline at 380 nm. The absorbance increases linearily with time after a lag-period of 30 seconds to 5 min. The reaction is followed for about 10 min. and the increase in absorbtion per min is calculated from the linear part of the absorbtion curve. The test could also be performed by taking 2 readings at about 5 min intervals.

In the studies of the enzyme kinetics a competitive inhibitor of the reaction was found in plasma. The amount of the inhibitory substances seemed to be nearly constant in the plasma samples studied from normal pregnant women as well as in plasma samples with high enzyme activity (twin-pregnancy) and low enzyme activity (severe pre-eclampsia).

The normal enzyme activity pattern showed an increase from about 210 days of pregnancy and towards the term. A coefficient of correlation of + 0.83 with the more time consuming method using l-cystine-di-βnaphtylamide as substrate was found. It was concluded that the present method could replace the method described by Babuna & Yenen (1966) at least from about 210 days of pregnancy and where a rapid answer is necessary.
THE MEASUREMENT OF HYPOTHALAMIC RELEASING HORMONE CONTENT AND ACTIVITY IN THE UNANAESTHETIZED RAT BY MEANS OF CAROTID ARTERY CANNULATION
Authors: Krause Robert , Syllwasschy-Anlauf Barbara
Published: December 2008

To gain insights into quantitative changes in hypothalamic substances which affect the function of the anterior hypophyseal lobe, we developed a technique for carotid cannulation allowing sequential measurements of plasma levels of an affected hormone after injection of such a factor. The principle involves the use of a previously cannulated rat in an unanaesthetized unstressed condition The hypothalamic extract or LH-RH injected into the cannulas of such animals leads to rapid peaks of LH in peripheral blood removed from the same cannulas within 6 to 8 min, followed by a slow decrease. At least 50% of the peak value is usually found within 3 min. The technique yields quantitatively reproducible results, and appears suitable for measuring relative potencies of test extracts against pure standards and, within as yet undetermined limits, for kinetic studies.
ASSESSMENT OF GH RELEASING HORMONE ACTIVITY IN SEPHADEX-SEPARATED FRACTIONS OF PORCINE HYPOTHALAMIC EXTRACTS BY HYPOPHYSEAL PORTAL VESSEL INFUSION IN THE RAT
Authors: Takahara Jiro , Arimura Akira , Schally Andrew V.
Published: December 2008

Growth hormone-releasing hormone (GH-RH) activity in Sephadex G-25 fractions of porcine stalk median eminence (SME) extracts was examined in vivo by infusing these samples into a rat hypophyseal portal vessel. The increment of immunoreactive GH levels in the serum was used as the index for GH-RH activity. The GH-RH activities were found in two different locations: in the early fractions Nos. 3–4, and in somewhat retarded fraction No. 7. These GH-RH activities were not due to TRH, vasopressin, or potassium. The location of LH releasing hormone (LH-RH) and prolactin release-inhibiting hormone (PR-IH) determined in this in vivo system was in agreement with those found in other in vivo and in vitro assay systems for LH-RH and PR-IH, respectively. These results help validate this assay system.
STUDIES ON THE INHIBITORY EFFECT OF SOMATOSTATIN ON GLUCOSE INDUCED INSULIN RELEASE IN THE ISOLATED PERFUSED RAT PANCREAS
Authors: Efendić S. , Luft R.
Published: December 2008

Somatostatin, the recently discovered growth hormone release-inhibiting hormone in the hypothalamus, also inhibited glucose induced insulin release from the isolated perfused rat pancreas. The lowest effective dose of somatostatin was 1 ng/ml of perfusate. By increasing the dose to 100 ng/ml an almost complete inhibition of basal as well as stimulated insulin release was obtained. The inhibition of glucose stimulated insulin release mediated by somatostatin might be of competitive nature since somatostatin seemed to dislocate the glucose-insulin dose-response curve to the right.
STUDIES ON THE MECHANISM OF SOMATOSTATIN ACTION ON INSULIN RELEASE IN MAN
Authors: Efendić S. , Luft R.
Published: December 2008

The present studies have demonstrated that the growth hormone release-inhibiting factor of the hypothalamus, somatostatin, exerts a prominent inhibiting action on glucose induced insulin release in man. This inhibition of insulin release could not be reversed by infusion of the α-adrenergic blocking agent, phentolamine. Our findings therefore suggest that the inhibiting effect of somatostatin on glucose induced insulin release is not mediated by the α-adrenergic receptors.
INSULIN COMPONENTS RELEASED BY THE NORMAL AND SUBTOTAL DEGRANULATED PERIFUSED ISLETS OF LANGERHANS OF THE RAT
Authors: Hermida O. García , Gómez-Acebo J.
Published: December 2008

The insulin components released from normal and tolbutamide treated islets of the rat were studied in a perifusion system. The treated islets showed diminished quantities of insulin secreted as compared to the controls and an increase in the proportions of "big insulin" secreted during the second phase of this release. On the other hand, the main component of insulin released during the first phase was "little insulin". These studies confirm that the subtotally degranulated islets are less efficient than the controls in producing insulin release.
PROGESTERONE-BINDING PROTEINS: IN VITRO BINDING AND BIOLOGICAL ACTIVITY OF DIFFERENT STEROIDAL LIGANDS
Authors: Kontula Kimmo , Jänne Olli , Vihko Reijo , de Jager Evert , de Visser Jacob , Zeelen Filippus
Published: December 2008

Progesterone-binding proteins from human, rabbit, sheep and guinea pig myometrial cytosol, all induced with oestradiol, as well as from pregnant guinea pig myometrium and plasma were investigated. The physico-chemical properties of the oestradiol-induced binding proteins were very similar in all the species studied.

In all, 63 steroids were tested for their ability to compete with tritiated progesterone for the binding sites on these six proteins and their relative affinities were determined. The studies reveal that the ligand specificities of oestrogen-induced myometrial binding proteins from human, rabbit and sheep are rather similar, whereas that from guinea pig myometrium has different binding characteristics. The properties of the binding proteins from pregnant guinea pig uterus and plasma differ substantially from all of the induced proteins. It is clear from the different physico-chemical characteristics and binding specificities that the oestrogen-induced myometrial protein of the guinea pig is not the same as that which appears in the myometrium and plasma during pregnancy.

The binding energies of the well bound progestational compounds were of the order of −12 Kcal/mole, half of which stems from the interaction of the steroid nucleus with the protein. The specific interaction of the protein with the two functional groups, the 3-keto-4-ene system and the acetyl side chain each contributed −3 Kcal/mole. In the case of the rabbit, sheep and human proteins a 17α-ethynyl-17β-hydroxyl function could replace the acetyl side chain.

For a large number of steroids reasonable agreement existed between the degree of binding to the rabbit myometrial protein and in vivo biological activity (Clauberg-McPhail test) in the same species. The data suggest that as far as the binding aspect is concerned, the rabbit is an appropriate model for assessing the biological activity of compounds under development for human application. The in vitro binding system is also a useful tool to assess whether steroids need to be bio-activated before eliciting a biological response.
PLASMA TESTOSTERONE IN KLINEFELTER'S SYNDROME: DIURNAL VARIATION AND RESPONSE TO ACTH AND DEXAMETHASONE
Authors: Smals A. G. H. , Kloppenborg P. W. C. , Benraad T. J.
Published: December 2008

The mean basal plasma testosterone level in 28 patients with chromatin positive Klinefelter's syndrome was significantly lower than in 58 healthy male controls. In 12 of the patients the hormone levels were in the normal range. In both the eugonadal males and the Klinefelter patients the plasma testosterone levels spontaneously decreased throughout the day, the relative decrease in both groups being of the same order of magnitude.

Short term ACTH infusion and the administration of dexamethasone did not significantly influence the plasma testosterone concentration in the Klinefelter patients. These findings do not support the view that the adrenal cortex plays a major role in contributing to the circulating plasma testosterone levels in this syndrome.
THE PLASMA PROLACTIN LEVELS IN MAN DURING PROLONGATION OF DARKNESS IN THE MORNING
Authors: Osterman P. O. , Wide L.
Published: December 2008

The plasma prolactin levels were studied in 4 healthy subjects with a constant sleep-waking cycle and a constant activity schedule before and after experimental alteration of the dark-light cycle. The subjects slept in the dark from 10.30 p. m. to 6.30 a. m. During a control period of 10 days the subjects stayed in rooms which were well lighted after 6.30 a. m. During the following 10 days darkness was prolonged by 4 hours until 10.30 a. m. Blood samples were obtained at 10.30 p. m., and each hour from 2.30 to 11.30 a. m. on days 9 and 10 of each period of investigation. In all the subjects an increase of the plasma prolactin level occurred during sleep. At about the time of waking the concentration fell rapidly. There was no apparent shift in the waking-related decrease in the prolactin level during the experimental period with extended darkness. Present data do not indicate that the dark-light transition in the morning is essential for the waking-related decrease in the prolactin level.
EFFECT OF OVARIECTOMY ON OESTROGEN-SENSITIVE FEEDBACK ELEMENTS
Authors: Zanisi M. , Martini L.
Published: December 2008

Serum LH and FSH were measured by radioimmunoassay in untreated and oestrogen-treated ovariectomized rats. The animals were sacrificed 7, 14, 21 and 28 days after ovariectomy. Oestradiol benzoate was administered in the daily dose of 50 μg on the 2 days preceding sacrifice. It has been found that oestrogens exert a strong inhibitory effect on the release of LH, as evidenced by a decrease in serum titers of the hormone. Oestradiol suppressed LH almost completely in animals with both low (7 or 14 days post-ovariectomy), and high levels of serum LH (21 or 28 days post-ovariectomy). Oestradiol failed to totally suppress serum FSH at any post-castration time considered. Moreover, the inhibitory effect of oestradiol on FSH release decreased as post-castration time increased. These data suggest that the feedback mechanisms which control the secretion of LH and those which control the secretion of FSH are substantially different.
THYROXINE METABOLISM IN THE RAT: EFFECT OF VARYING DOSES OF EXOGENOUS THYROXINE
Authors: Galton Valerie Anne
Published: December 2008

Experiments were performed to determine quantitatively the peripheral metabolism of exogenous thyroxine T4) in rats brought to isotopic equilibrium with doses of 131I-T4 ranging from 1 to 20 μg/100 g body weight/ day. It was found that, although the absolute amount of T4 either deiodinated and excreted as iodide in urine or excreted as T4 in faeces increased as the dose of T4 increased, the percentage of hormone excreted by either pathway at each dose level was relatively constant. In other words, the fractional rate of deiodination is not greatly influenced by the amount of T4 administered. A 20-fold increase in the dose of T4 resulted in only a 4-fold increase in serum T4 concentration measured 24 h after injection, but serum T4 levels were elevated considerably more than this for several hours between injections. Nevertheless, the highest dose of T4 was not greatly thyrotoxic. The implications of these findings in relation to the possible association between the metabolism and action of T4 are discussed.
16-DEHYDROGENASE IN HUMAN PLACENTA
Authors: Preumont P. , Smuk M.
Published: December 2008

Human placental subfractions were incubated with radioactive oestriol and 16-oxo-oestradiol*. 16-oxo-oestradiol was identified from the oestriol incubation. Oestriol and 16-epi-oestriol were characterized from the incubation with 16-oxo-oestradiol. The 16α-dehydrogenase has been located in the soluble fraction (105 000 g supernatant) of the human placenta.
PRESENCE OF "RECEPTORS" FOR GROWTH HORMONE ON MEMBRANES OF RAT THYMOCYTES
Authors: Pandian M. R. , Gupta P. D. , Talwar G. P. , Avrameas S.
Published: December 2008

Growth hormone conjugated to Sepharose-4 B was found to mimic the action of the free hormone in the stimulation of the uptake and incorporation of radioactive uridine into RNA in thymocytes in vitro. The integrity of the cellular structure was essential for the stimulating effect of the hormone. The binding of the immunologically reactive determinants of the hormone on membranes of thymocytes was demonstrated by electron micrographs of preparations incubated sequentially with rabbit antigrowth hormone globulins and monospecific sheep anti-rabbit globulins tagged with horse-radish peroxidase.
METABOLITES OF LYNESTRENOL ACETATE IN THE BILE OF RATS AFTER INTRAVENOUS ADMINISTRATION; A COMPARISON WITH LYNESTRENOL
Authors: Coert A. , Geelen J. , van der Vies J.
Published: December 2008

Some aspects of the metabolism of lynestrenol acetate, an orally active contraceptive compound, were studied in female rats. Lynestrenol acetate is stable in gastric and intestinal juice in vitro. After intravenous administration of lynestrenol acetate and lynestrenol with a 14C label in the nucleus approximately 40 % of the administered radioactivity was excreted in the bile within 90 min. After administration of lynestrenol acetate labelled in the ester group, 6% of the radioactivity was found in the bile. This means that the greater part of the lynestrenol acetate had lost its acetate group during the process of metabolism.

There was an important difference between the autoradiograms of the thin layer patterns of post-hydrolysis extracts after administration of [4-14C]lynestrenol acetate and those after administration of [1′-14C]lynestrenol acetate and [4-14C]lynestrenol: the major metabolite of [4-14C]-lynestrenol acetate did not appear on the autoradiograms of [1′-14C]lynestrenol acetate and [4-14C] lynestrenol. This indicates that lynestrenol acetate was altered in the nucleus in the presence of the acetate group. The acetate group itself was removed, either when the alteration took place, or after it had been completed. The results of IR, NMR and mass spectrometry analysis indicate the introduction of a 15α hydroxyl group. Results of gas-liquid chromatography and thin layer chromatography indicate that a second important metabolite is 19-nor-17α-pregn-20-yne-3α, 17β-diol. The main conclusions are:

A part of the lynestrenol acetate is metabolized and excreted in the bile, the acetate group still being present.

Lynestrenol acetate is to some extent metabolized via another pathway than lynestrenol. This indicates that esterification of a steroid can lead to deviation from the metabolic pathway of the free original steroid.
AGE DEPENDENT CHANGES IN IODINE METABOLISM AND THYROID FUNCTION
Authors: Hansen J. Mølholm , Skovsted Lis , Siersbæk-Nielsen K.
Published: December 2008

Absolute iodine uptake (AIU), serum thyroxine (T4), free T4 index and serum triiodothyronine (T3) were studied in 48 women and 63 men aged 20 to 90 years. AIU decreased with age in both sexes to values in the oldest age groups of about 60 % of the values in the youngest age groups. AIU values for females were about 75 % of the values for males. Free T4 index was found to be unaltered with increasing age but serum T3 decreased with age. These findings and the previous demonstrated decrease in T4 degradation rate seem consistent with the assumption that T4 and T3 production decreases with advancing age.
GLUCOSE INHIBITION OF THE PERMEATION OF CHLOROMERCURIBENZENE-P-SULPHONIC ACID IN THE PLASMA MEMBRANE OF PANCREATIC β-CELLS
Authors: Söderberg Monica
Published: December 2008

The transport of chloromercuribenzene-p-sulphonic acid (CMBS) was studied in microdissected pancreatic islets of ob/ob mice incubated in Krebs-Ringer bicarbonate medium. Glucose inhibited the islet uptake of CMBS. The initial binding of CMBS to superficial thiol groups was inhibited to a lesser extent than was its further permeation into the interior of the plasma membrane. The non-metabolized glucose analogue 3-0-methyl glucose had no effect on the permeation of CMBS. Whereas mannoheptulose, epinephrine and diazoxide lacked any effect in themselves, they tended to counteract the glucose inhibition of CMBS permeation. The ability of glucose to inhibit CMBS permeation is related to its insulin-releasing action rather than to its membrane transport or further metabolism.
A TRANSDUCER PROBE FOR THE DETECTION OF OESTROGEN EFFECTS ON VAGINAL BLOOD FLOW IN SHEEP
Authors: Benoit Henry J. , Borth Rudi , Woolever C. Allan
Published: December 2008

A simple prototype vaginal probe was designed for the electronic detection of oestrogen-induced blood flow changes by measuring thermal conductivity, tissue temperature, and light reflectance. The probe was tested in six castrate ewes. Treatment with oestradiol-17β (1.0 mg, iv) produced marked changes in thermal conductivity and temperature, but had no detectable effect on reflectance. The study demonstrates the feasibility of multiple-sensor electronic probes for non-invasive monitoring of peripheral oestrogen effects in vivo.
RECEPTORS MEDIATING EPINEPHRINE EFFECT ON THYROID 131I UPTAKE AND THYROXINE SYNTHESIS IN THE RAT
Authors: Joasoo A. , Murray I. P. C.
Published: December 2008

The adrenergic receptors mediating the inhibitory effect of epinephrine on the rat thyroid in vivo have been studied by the use of more specific alpha- and beta-adrenergic stimulators, and blocking agents. The effect of methoxamine was similar to that of epinephrine, while isoproterenol stimulated 131I uptake slightly, and did not alter the ratio of monoiodotyrosine (MIT) to diiodotyrosine (DIT). However, like methoxamine, isoproterenol resulted in a decrease in thyroxine (T4) formation. Phentolamine could partially prevent epinephrine-induced decrease in 131I uptake and T4 synthesis. The changes in the MIT/DIT ratio could be completely prevented by high doses of phentolamine. Propranolol enhanced the effects of epinephrine. It is concluded that the effect of epinephrine on the rat thyroid in vivo is predominantly alpha-adrenergic, but T4 synthesis may be decreased by stimulation of either receptor.
THE INFLUENCE OF SHORT TERM SUBMAXIMAL WORK ON THE PLASMA CONCENTRATIONS OF CATECHOLAMINES, PANCREATIC GLUCAGON AND GROWTH HORMONE IN MAN
Authors: Nilsson Karl Olof , Heding Lise G. , Hökfelt Bernt
Published: December 2008

Studies were performed in 6 healthy, male volunteers to explore the effect of a work load on the blood concentrations of catecholamines in relation to pulse rate and blood pressure and the blood levels of pancreatic glucagon, insulin, growth hormone, glucose and glycerol. The work load consisted of 300 kpm/min for 5 min, followed by 600 kpm/min during the next 5 min and 900 kpm/min under a third 5 min period.

The work load resulted in a marked increase in noradrenaline and adrenaline at 10 and 15 min of exercise. The pulse rate, the systolic pressure and the mean blood pressure were correlated to the blood levels of both adrenaline and noradrenaline.

In spite of the rather marked activation of the sympathetic nervous system no increase occurred in glucagon as measured under exercise and up to 60 min after its completion. In 4 of the subjects the work load was followed by a prompt growth hormone response. The same 4 subjects also showed a marked increase in catecholamines. The 2 remaining subjects presented no change in growth hormone and their increase in catecholamines was relatively minor.

Glycerol increased significantly during work and there was a positive correlation between the values recorded for glycerol and adrenaline.

No significant changes occurred in blood sugar or insulin during work.
COMBINATION CONTRACEPTIVE EFFECTS ON MONTHLY CYCLE OF PLASMA ALDOSTERONE, RENIN ACTIVITY AND RENIN SUBSTRATE
Authors: Katz Fred H. , Romfh Peggy , Smith Judith A. , Roper Ellen F. , Barnes John S.
Published: December 2008

A post-ovulatory peak of fasting supine plasma aldosterone (PA) preceded or accompanied by an increase in plasma renin activity (PRA) was previously reported. These studies have now been extended in 4 additional normal menstruating women and 4 women taking oestrogen-progestogen oral contraceptive pills (OCP), all studied daily for an entire cycle. Distinct luteal phase increases in PRA were seen in the 4 normals, with 2 also demonstrating a rise in PA. Plasma renin substrate (PRS) was usually unvarying throughout the control cycles. The women taking OCP, on the other hand, all had PA and PRA peaks that were apparent by the fourth or fifth day of taking "the pill". All 4 of the treated women had elevated PRS levels but only one woman showed an increase which preceded the elevation of PRA and PA. Plasma cortisol levels were usually above the normal range in the women taking OCP. This study thus indicates that factors other than oestrogen-induced increased substrate production may be responsible for the PRA and PA rise during OCP treatment Such factors might be the natri-uretic effects of oestrogens and progestogens or a direct effect on renin secretion by one of these steroids.
THE ONTOGENY AND REGULATION OF CORTICOSTEROID SECRETION BY THE OVINE FOETAL ADRENAL
Authors: Wintour E. Marelyn , Brown Elizabeth H. , Denton D. A. , Hardy K. J. , McDougall J. G. , Oddie Catherine J. , Whipp G. T.
Published: December 2008

Adrenal glands of foetal sheep of 40 days gestation to term were incubated with and without ACTH or an increased [K+]. With ACTH, the 40 day foetal adrenal was capable of producing more cortisol and aldosterone per g body weight than was the term adrenal. ACTH was a potent stimulus to aldosterone and cortisol production in foetuses aged 60–90 days, and this effect declined significantly in the 91–120 day period. An increased [K+] was stimulatory to aldosterone production only after 120 days gestation. Peripheral blood levels of aldosterone, corticosterone, cortisol, 11-deoxycortisol and 11-deoxycorticosterone were measured in foetuses 60 days to term and the levels of aldosterone and cortisol were significantly lower in 90–120 day foetuses than in the younger or older ones. Direct adrenal vein cannulation proved all five steroids to be secretory products of the foetal adrenal.
EFFECT OF POST-OVULATORY ADMINISTERED OESTROGENS ON CORPUS LUTEUM FUNCTION
Authors: Lehmann F. , Just-Nastansky I. , Behrendt B. , Czygan P.-J. , Bettendorf G.
Published: December 2008

The effect of orally given diethylstilboestroldiphosphate (DES) and 17α-ethinyl-oestradiol-3-methylether (EEM) on plasma progesterone levels was studied. Both compounds were administered for 5 days to 5 women in daily doses of 60 mg (DES) and 30 mg (EEM). The fully informed volunteers were found to have a normal menstrual cycle before the study. The mean corpus luteum phase (corpus luteum phase = days between LH surge and onset of menstruation) of all control cycles lasted 12.8 days. Daily plasma samples were collected for radioimmunoassay (RIA) of progesterone, immunoreactive oestrogens and LH. After a control cycle the first treatment was carried out with DES. The third and the fifth cycle were control cycles again. The EEM-treatment was done in the fourth cycle. Although the effect of the two compounds was different, a dependence of the age of the corpus luteum (CL) could be demonstrated for both. DES-treatment lowered plasma progesterone levels during administration. This effect was only demonstrable if the treatment was begun on the day of the LH-peak. The length of the CL-phase remained unaltered. EEM-treatment if started on the day of the LH surge, suppressed corpus luteum function in the late luteal phase. If the treatment was started later, the effect was less pronounced. The administration of both compounds did not shorten the time between ovulation and the next bleeding. After DES-treatment this interval was not altered. After EEM-treatment the subsequent bleeding was even delayed depending on slowly decreasing levels of plasma oestrogens.
PLASMA DIHYDROTESTOSTERONE IN NORMAL ADULT MALES AND ITS RELATION TO TESTOSTERONE
Authors: Pirke Karl M. , Doerr Peter
Published: December 2008

A radioimmunoassay for dihydrotestosterone (DHT) in plasma was developed using an antiserum raised against testosterone-3-oxime-bovine-serum-albumin. After extraction of 1 ml male plasma with diethylether, DHT was separated from testosterone (T) by thin-layer chromatography. A dextran-charcoal-suspension was used for the separation of bound and free ligand. The inter-assay variability was 10.4 % (C. V.) and the detection limit 1.77 ng/100 ml. The accuracy of the method as determined by mass recoveries and the specificity were shown to be satisfactory.

Normal values were obtained in 45 young to middle-aged (22–61 years) and 37 old (68–93 years) men. The median and the 95 percentiles were 20.5–51.9–76.3 (ng/100 ml) and 19.5–50.9–101.5 (ng/100 ml) respectively. While DHT did not change in old age T fell by 20.6%. DHT and T showed a significant correlation: rS = 0.426, P < 0.01 (young men), rS = 0.752, P < 0.001 (old men).

After 3 daily im injections of 5000 IU human chorionic gonadotrophin (HCG), DHT increased 1.50 times (range: 1.15–2.09, n = 12), T 1.86 times (range: 1.20–2.91, n = 12). After 4 daily administrations of 40 mg fluoxymesterone DHT fell to 29.6% of the control level (range: 16.0–48.2%, n = 12).

Blood samples were obtained from a 24 year old man every 15 min for 24 h. A close parallelism was observed between the concentrations of DHT and T in the plasma.
PLASMA ANDROGEN LEVELS IN MEN AFTER ORAL ADMINISTRATION OF TESTOSTERONE OR TESTOSTERONE UNDECANOATE
Authors: Nieschlag E. , Mauss J. , Coert A. , Kićović P.
Published: December 2008

Plasma testosterone and androstenedione levels in men were measured after oral administration of free testosterone and testosterone undecanoate. Both androgens were determined by simultaneous, specific radioimmunoassays after separation and isolation by thin layer chromatography.

While free unesterified testosterone had no effect on plasma androgen levels, a striking increase of both testosterone and androstenedione levels was noted after administration of testosterone undecanoate, which is otherwise only achieved by parenteral testosterone application. This effect of testosterone undecanoate is probably due to absorption via the lymph rather than via the portal vessels so that peripheral circulation is reached before metabolism in the liver. Testosterone undecanoate promises to be an effective medication for oral androgen replacement.
EFFECT OF TRANSPLANTATION OF THE FOETAL TESTIS TO NEONATAL FEMALE RATS ON DIFFERENTIATION OF THE POSTPUBERTAL SECRETORY PATTERN OF GONADOTROPHIN
Authors: Arai Y. , Serisawa K. , Kigawa A.
Published: December 2008

Rat foetal testes (day 19 or 20 pregnancy) were transplanted into the neck of 3-day-old female rats. When testicular grafts were left in the recipients until autopsy (at 90 days of age), anovulatory persistent oestrous syndrome developed in most of the recipient females. These changes were not influenced by the removal at 45 days of age of the testicular grafts. However, the incidence of anovulatory sterility was significantly reduced when the foetal testicular grafts had been removed 5 days after transplantation. Treatment of these recipient females with 40 IU HCG from the day of the transplantation to the day before the removal of the transplants markedly increased the incidence of anovulatory sterility in the recipient females. In histological examinations of the testicular grafts upon their removal, a significant stimulation of Leydig cell elements was noted in the groups of rats treated with HCG. It is highly probable that if sufficient levels of gonadotrophin (GTH) are present in the recipient females, testicular tissues from day 18–20 foetuses can secrete sufficient amounts of androgen for masculinizing GTH regulation.
CORRELATION OF DIAMETERS OF SECRETORY GRANULES IN CLINICALLY NON-FUNCTIONING CHROMOPHOBE ADENOMAS OF THE PITUITARY WITH THOSE OF NORMAL THYROTROPHS
Authors: Gray A. B. , Doniach I. , Leigh P. N.
Published: December 2008

Diameters of secretory granules in thyrotrophs and in gonadotrophs were measured in electron micrographs of operation specimens of 4 pituitary glands and of the secretory granules in operation specimens of 10 clinically non-functioning chromophobe adenomas. The mean diameter of the thyrotroph granules was 137 ± 26 nm, of the gonadotrophs 204 ± 38 nm, of 9 of the adenomas 141 ± 20 nm and of the remaining adenoma 248 ± 67 nm. The significance of the close correlation in granule size in most of the adenomas with that of thyrotrophin granules is discussed briefly.
POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN
Authors: Cerasi Erol
Published: December 2008

The effect of repeating a 60 min glucose infusion at a 40 to 70 min interval was investigated after an overnight fast in 14 healthy, non-obese subjects with normal glucose tolerance and normal insulin response to glucose administration. When a hyperglycaemic plateau of around 300 mg/100 ml was induced by the first glucose infusion, the insulin response to a second challenge was enhanced over the range of stimulations used. Both the early and late phase insulin responses were amplified, the enhancement being more marked with higher stimulatory levels of glucose. The blood glucose-insulin dose-response curve became steeper after pretreatment with glucose, the stimulatory threshold level not being altered. These findings suggest that the synergism between the glucose pretreatment, and the insulin releasing effect of glucose, is of multiplicative type, resulting in increase of the maximum effect of the glucose.

The dose-dependency of this potentiation was investigated by keeping the second glucose challenge at a constant level and altering the dose of the first infusion. It was necessary to reach hyperglycaemias around and above 300 mg/100 ml during the first infusion in order to obtain enhancement of the insulin response to the second stimulus. The dose-response curve of the potentiating effect of glucose is thus displayed towards the right when compared with that describing the insulin releasing effect of glucose, which has its threshold around 100 mg/100 ml.

It is suggested that glucose exerts a dual effect on the pancreatic islets: an immediate one which initiates the release of insulin, and a time-bound one which modulates the first action.
POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN
Authors: Cerasi Erol
Published: December 2008

If two consecutive glucose infusions are administered with 40 min of rest between, the insulin response to the second challenge is markedly potentiated. When the insulin response to the first glucose infusion was suppressed by 65 % with the aid of adrenaline, potentiation of the insulin response to the second infusion was not modified. This suggests that the generation of a state of enhancement in the islet does not necessitate that glucose exerts its insulin releasing action. It is postulated that islet glucose metabolism may be involved in producing the potentiation.

Pretreatment of the subjects with a glucose infusion enhanced also the insulin responses to glucagon and to tolbutamide, given intravenously 50 min later. Thus, the potentiation generated by glucose is not restricted to the insulinogenic signal induced by glucose. The eventual role that the beta-cell adenylate cyclase may play in this respect is discussed.
THE EXCRETION OF INDIVIDUAL ADRENOCORTICAL STEROIDS DURING NORMAL CHILDHOOD AND ADOLESCENCE
Authors: Savage D. C. L. , Forsyth Constance C. , McCafferty Eileen , Cameron Jenny
Published: December 2008

The excretion of 7 individual 17-oxosteroids and 7 individual corticosteroids in 24 h urine samples from 62 normal infants, children and adolescents, based on an accurate and specific paper chromatographic method for their separation and quantitation, is reported. The excretion of the 11-deoxy-17-oxosteroids gradually increases from 7 years of age and the increase becomes more rapid 2 or 3 years before the clinical signs of puberty appear. The rise continues throughout puberty and beyond it until the adult level is reached. The increase far exceeds that which would be accounted for by the growth of the individual. The increase in the excretion of the 11-oxy-17-oxosteroids with age is much more gradual. Androgens favour the formation of 5α metabolites and the 5α:5β ratio of the total 5α 17-oxosteroids and the total 5β 17-oxosteroids shows a statistically significant increase with age. In addition, a relatively high 5α:5β ratio is noted in male infants, which is likely to be related to their relatively high plasma testosterone levels. The excretion of the 17-hydroxycorticosteroids and the α-ketolic metabolites of cortisol gradually rises with age and correlates with body weight. The α-ketolic metabolites of corticosterone are relatively high in infancy, but after the age of 4 years their excretion also correlates with body weight. An increase in the 5α:5β ratio of allo-THF to THF is noted at puberty similar to that found with the 5α:5β ratios of the 17-oxosteroids.
THE LH-hCG RECEPTOR OF HUMAN OVARY AT VARIOUS STAGES OF THE MENSTRUAL CYCLE
Authors: Wardlaw S. , Lauersen N. H. , Saxena B. B.
Published: December 2008

Receptors specific for hCG were found in human corpora lutea and follicles. hCG and LH were found to bind at a similar receptor site. The dissociation constant for hCG ranged from 10−10 to 10−11 mol/l in human corpora lutea. The number of binding sites for 125I-hCG ranged from 10−14 to 10−15 moles/mg protein in human corpora lutea. The binding of 125I-hCG to ovary was found to vary at different stages of the menstrual cycle. The binding of 125I-hCG to human ovaries increased on days 13–15 of the cycle, then declined slightly, and increased again on days 22–23. Following day 23, there was a slow decline until day 27 when binding activity could no longer be measured. No binding could be measured by the corpus luteum after the onset of menstruation or in corpora albicans.
IMPLANTATION AND MAINTENANCE OF PREGNANCY IN MATED RHESUS MONKEYS FOLLOWING BILATERAL OOPHORECTOMY OR LUTEECTOMY WITH AND WITHOUT PROGESTERONE REPLACEMENT
Authors: Bosu William T. K. , Johansson Elof D. B.
Published: December 2008

Six mated rhesus monkeys were bilaterally oophorectomised between the fourth and sixth day after ovulation, and received silastic implants containing crystalline progesterone subcutaneously. Five mated monkeys were subjected to luteectomy 5 or 6 days after ovulation. Three of these received progesterone implants subcutaneously. Pregnancy occurred in one oophorectomised monkey and in all three luteectomised monkeys treated with progesterone. It was evident from the steroid patterns observed in the pregnant monkeys that the ovarian tissue other than the corpus luteum contributes to part of the oestrogen seen around the time of implantation. The corpus luteum appears to be the main source of progesterone in the peripheral plasma during this period. Placental progesterone production in early pregnant rhesus monkeys starts at three weeks after ovulation and the placental production of progesterone precedes that of oestrogen.
THE EFFECTS OF LH-RH ON THE CONCENTRATION OF 3′,5′-CYCLIC AMP AND RNA SYNTHESIS IN RAT ANTERIOR PITUITARY
Authors: Yoshida Takeshi , Hattori Yutaka , Hoshiai Hiroshi , Hirano Mutsuo , Takahashi Katsuyuki , Suzuki Masakuni
Published: December 2008

In an experiment performed to investigate the effect of LH-RH on the anterior pituitary of rats, we studied the changes in the concentration of 3′,5′-cyclic AMP in the anterior pituitary and the uridine uptake by the anterior pituitary following the intravenous injection of 100 ng LH-RH. The results obtained are summarized as follows: 1) The tissue level of 3′,5′-cyclic AMP in the anterior pituitary reached the highest peak 15 min after the injection of LH-RH. 2) The uridine uptake of the anterior pituitary began to increase 15 min after the LH-RH injection and attained a maximum level (5 to 6 times the normal level) in 30 min. 3) The fact that the uridine uptake was inhibited to a considerable extent by the addition of actinomycin D to the incubation medium suggested that uridine was incorporated into the RNA fraction.
PARTIAL FAILURE OF ANTERIOR PITUITARY AND THYROID PRESENTING AS MYXOEDEMA
Authors: Toft A. D. , Irvine W. J.
Published: December 2008

The development of a sensitive radioimmunoassay of plasma thyrotrophin (TSH) and the isolation and synthesis of thyrotrophin-releasing hormone (TRH) allows a precise evaluation of the disordered brain-thyroid axis. The present report describes a patient who presented with myxoedema due to partial failure of both the anterior pituitary and the thyroid gland. The degree of impaired function of either gland alone would not have caused her clinical presentation.
OPHTHALMOPATHY ASSOCIATED WITH PRIMARY HYPOTHYROIDISM
Authors: Brownlie B. E. W. , Newton O. A. G. , Singh S. P.
Published: December 2008

Ten patients with primary hypothyroidism and ophthalmopathy are reported. None of the patients had previously received any form of therapy for thyrotoxicosis. In some patients hypothyroidism and exophthalmos presented simultaneously, but in others one clinical feature preceded the other by many years. Elevated titres of thyroid antibodies were found in 7 of the 10 patients and LATS was detected in 1 of the 10 patients. Increased 35S-sulphate uptake by the mouse Harderian gland technique occurred with serum from I of the 7 patients tested.
STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY
Authors: Søvik Oddmund , Oseid Svein
Published: December 2008

Suppressible and non-suppressible insulin-like activities (ILA) of plasma from 3 patients with congenital generalized lipodystrophy have been studied, employing isolated fat cells from rat epididymal adipose tissue.

In all 3 patients the fasting ILA was markedly increased compared with the normal controls. In one of the patients (I. T.) total ILA rose to about 800 μU per ml during an iv glucose tolerance test.

The observed total ILA was in all cases (controls included) equal to or slightly higher than the previously determined immunoreactive plasma insulin (IRI). The exact determination of ILA was, however, hampered by a dilution effect, which was present even at high plasma dilutions.

In 2 of the patients addition of insulin antiserum inhibited plasma ILA by about 50 %. In the third patient (I. T.), who exhibited the highest insulin level, at least 85 % of the activity was suppressed by insulin antibodies. The levels of non-suppressible ILA were higher than in the controls in terms of μU per ml, but lower than in the controls when related to total ILA.

These findings strongly support our previous conclusion that the elevated plasma insulin seen in congenital generalized lipodystrophy is mainly due to true pancreatic insulin.

Since the effect of plasma insulin on isolated fat cells were freely expressed, i. e. suppressible ILA was equal to or slightly lower than IRI, the presence of a circulating insulin antagonist in this disease may be excluded.
SUBUNITS OF HUMAN CHORIONIC GONADOTROPHIN: IMMUNOLOGICAL AND BIOLOGICAL STUDIES
Authors: Donini S. , D'Alessio I. , Donini P.
Published: December 2008

The α and β subunits of human chorionic gonadotrophin (hCG) were prepared by incubation in 8 m urea, pH 4.5. The separation of the two subunits was obtained by DEAE-Sephadex A-25 chromatography and purification was carried out by gel filtration on Sephadex G-100. The β subunit obtained was biologically active and was therefore further purified by affinity chromatography using as immuno-adsorbent the α antibodies coupled to Sepharose 4B. The β subunit so purified showed a biological activity less than 1 IU/mg.

The immunological and biological properties of the hCG subunits have been studied. It was found that the anti hCG β serum can discriminate between hCG and hLH and that in the 125I-hCG + anti-β serum radioimmunoassay, the cross-reactivity of pituitary hLH was lower than that of urinary hLH. Moreover, it was observed that the less purified was the urinary LH preparation, the higher was the cross-reactivity. Therefore we considered the hypothesis that during the purification of human menopausal gonadotrophin (hMG) some LH subunits or smaller immunoreactive fragments could have been discarded with the waste fractions. In order to test the validity of this hypophysis, all the protein fractions obtained during the purification of the hMG were gel-filtered on Sephadex G-100. The immunoreactivity of the effluents from the gel filtration was tested by hCG, hCG-β, hCG-α and hLH radioimmunoassays. While the α reactive material was found in some fractions as a peak having the same Ve/Vo value as hCG-α, the β reactive material present in the crude hMG fractions was not observed in other fractions. The cross-reactivity with the anti β serum was very low and was found in the LH region of the gel chromatogram. Furthermore, the neutralization of the biological activity of hCG and of urinary and pituitary LH by the anti hCG β serum was studied by incubating a fixed amount of the three hormones with increasing volumes of antiserum and measuring the LH activity after incubation by the OAAD test. It was observed that the anti hCG β serum inhibits hCG more than urinary or pituitary LH.