bluuebunny/crossref_metadata_2025 huggingface dataset:
RECIPROCAL EFFECTS OF THYROXINE AND TRIIODOTHYRONINE ON THEIR DEIODINATION BY RAT TISSUES IN VITRO
Authors: Zaninovich Angel A.
Published: December 2008

The reciprocal effects of loading doses of thyroxine (T4) or triiodothyronine (T3) on the deiodination of their 125iodine-labelled isotopes by rat muscle and liver homogenates were studied. In 21 experiments muscle homogenates deiodinated a mean 45.0 % of a tracer dose of [125I]T4 and 18.0% of [125I]T3. On addition of graded amounts of non-radioactive T4 or T3 the percentual deiodination of both labelled hormones progressively declined. This effect was significantly greater in homogenates incubated with non-radioactive T4, thus reflecting a stronger affinity of this hormone for muscle deiodinating sites. This correlate with the greater displacement of [125I]T3 as revealed by the percentage of recovered labelled hormone. In 18 experiments liver homogenates deiodinated a mean 14.6% of a tracer amount of [125I]T4 and 8.5% of [125I]T3. The addition of a T4- or a T3-load was followed by a smaller decrease in percentual deiodination of both labelled hormones as compared to muscle homogenates. Unlike the effects observed in muscle, the breakdown of [125I]T4 and [125I]T3 by liver homogenates was equally affected by similar amounts of stable T4 or T3. It is concluded that in the present in vitro system T4 and T3 share cellular sites of deiodination in rat muscle and liver and that, at least in muscle, which constitutes over one-half of the rat body weight T4 appears to be preferentially deiodinated.
THYROID PEROXIDASE ACTIVITY IN IODINE DEFICIENT RATS
Authors: Fragu P. , Nataf B. M.
Published: December 2008

The evolution of peroxidase activity was followed during the course of iodine deficiency in the rat. The enzymatic activity was determined in vitro by oxidation of iodide or by iodination of bovine serum albumin using a peroxide-generating system.

An inverse relationship between the stable iodine content in the gland and the peroxidase activity is observed; this relation is not linear and the highest increase is found when the iodine content in the gland is below 5 μg per thyroid gland, at 35 days of the treatment.

In animals maintained on a low iodine diet, a triphasic effect on enzymatic activity is observed: early (10 and 20 days) and late (70 and 80 days) effects when the increase in peroxidase activity is 3 times higher than the increase in weight, DNA and total protein content; and an intermediar effect (between 20 and 70 days) when the peroxidase activity stays approximately at the same level. In any case, the enzymatic activity increases to a greater extent than do thyroid weight, and total protein and DNA content, suggesting that high cellular activity is due to a specific enzyme induction comparable to that we obtained recently in human sporadic goitre.
PLASMA INSULIN AND GROWTH HORMONE CONCENTRATIONS IN PREGNANT SHEEP I:
Authors: Hove Knut , Blom Anne Kristine
Published: December 2008

Two or three foetal lambs regularly result in a varying degree of carbohydrate shortage in mother ewes in late pregnancy. We have investigated the correlation between plasma insulin, growth hormone and energy substrate concentrations in ewes 8 and 1 weeks before lambing.

Plasma growth hormone was fairly constant (2–3 ng/ml) throughout the 24-h cycle 8 weeks before parturition. Seven weeks later higher average levels and increased diurnal fluctuations were observed in 3 out of 4 multiparous ewes. The average post-absorptive insulin levels were reduced by 50 per cent during the same interval. Simultaneously decreased post-absorptive sugar and increased acetoacetate levels were observed. It is concluded that the hormonal adaptations to the increasing carbohydrate deficit in late pregnancy, especially among multiparous ewes, include:

a) reduced post-absorptive plasma insulin levels,

b) reduced insulin responses to feeding, and

c) increased levels of growth hormone in the plasma.
IN VITRO SYNTHESIS OF STEROIDS BY A FEMINISING ADRENOCORTICAL CARCINOMA: EFFECT OF PROLACTIN AND OTHER PROTEIN HORMONES
Authors: Millington D. S. , Golder M. P. , Cowley T. , London D. , Roberts H. , Butt W. R. , Griffiths K.
Published: December 2008

The study describes the effects of ACTH, prolactin and other protein hormones on the synthesis and secretion of steroid hormones by tissue from a feminising adrenocortical carcinoma removed from a post-menopausal female. Steroid production by the tissue was determined by high resolutionmass fragmentography and by radioimmunoassay. Prolactin and ACTH stimulated the synthesis of oestrogens by the tissue whereas GH, LH and ACTH were more effective than prolactin in stimulating androgen synthesis. The effect of protein hormones, other than ACTH, on adenylate cyclase activity of this tumour tissue indicated a lack of specificity of the membrane receptor sites.
THE NORMAL DEVELOPMENT OF THE OVARY IN CHILDHOOD
Authors: Peters Hannah , Himelstein-Braw Ruth , Faber Mogens
Published: December 2008

The development of the ovary during childhood has been evaluated in 52 organs obtained from autopsy of children who died in accidents or after a brief acute disease. The ovaries at all ages showed follicle growth. 93% of the organs were actively growing ovaries containing healthy and degenerating follicles in progressive stages of development with and without follicle fluid. Three ovaries showed follicle growth up to pre-antral stages. None of the 52 ovaries were quiescent in which follicle development was not in progress. It is therefore argued that the normal ovary in childhood shows follicle growth at all ages. The number and size of antral follicles increases after the age of 6 years coinciding with the progressive increase in FSH and oestrogen output in childhood.
TESTOSTERONE PRODUCTION BY ISOLATED RABBIT FOLLICLES IN THE PRESENCE OF LUTEINIZING HORMONE AND INHIBITORS OF STEROIDOGENIC ENZYMES
Authors: YoungLai E. V.
Published: December 2008

Rabbit ovarian follicles were incubated with luteinizing hormone (LH) and various inhibitors of steroidogenesis in order to determine what enzymes were necessary for testosterone production. Incubations were carried out in minimum Eagle's medium: normal rabbit serum: 95: 5 with medium being changed every 15 min and stored at −15° C until assayed for testosterone by radioimmunoassay. Inhibitors and LH were added at different times after the start of the incubations. Of the inhibitors tested only SU 10603, an inhibitor of the 17α-hydroxylase enzyme completely prevented the testosterone response to LH while aminoglutethimide (inhibitor of 20α-hydroxycholesterol dehydrogenase) and U 30870 (inhibitor of 3β-hydroxysteroid dehydrogenase) only showed partial inhibition. These results suggest that cholesterol is an obligatory intermediate for the production of testosterone by rabbit ovarian follicles and that normal LH stimulated endocrine function can resume after treatment with inhibitors. The results are also in agreement with previous data using inhibitors of protein synthesis in the presence of LH.
EFFECTS OF TESTOSTERONE PROPIONATE TREATMENT OF NEONATALLY OVARIECTOMIZED RATS ON GROWTH AND SUBSEQUENT RESPONSIVENESS TO OESTROGEN
Authors: Tarttelin M. F. , Shryne J. E. , Gorski R. A.
Published: December 2008

There was no significant difference in body weight between neonatally ovariectomized (OvX) rats whether given oil treatment or 90 μg testosterone propionate (TP) on day 3, when examined up to 23 weeks of age. When these two animals were injected with oestradiol benzoate (3 μg/day for 2 weeks), the neonatally OvX TP treated rats showed a significantly smaller depression in body weight than did the control neonatally OxX rats. Measurement of food intake also showed that TP treated rats responded significantly less to the depressant effects of oestrogen than did the controls. These data are consistent with the hypothesis that the ovary does restrain body weight in TP rats but that androgen treatment in the neonatal period may not have a specific effect on growth but may alter the sensitivity of growth regulating processes to the inhibitory effects of oestrogen.
OESTRADIOL STIMULATION OF PROLACTING RELEASE FROM CANINE PITUITARY IN CULTURE
Authors: Jones Gwyneth E. , Boyns A. R.
Published: December 2008

Anterior canine pituitaries were maintained in tissue culture for 8 days, and the immunoreactive prolactin released, was measured by a heterologous radioimmunoassay for canine prolactin. Luteinizing hormone-releasing hormone (LH-RH) and thyrotrophic hormone-releasing hormone (TRH) did not affect prolactin release, while theophylline and oestradiol-17β stimulated the release of canine prolactin.
THE DEIODINATION OF THYROXINE IN HYPERTHYROID RATS AS DETERMINED BY RENAL CLEARANCE OF IODIDE
Authors: Edwards Brian R. , Stern Paul , Stitzer L. Kent , Galton Valerie Anne
Published: December 2008

Other investigators have reported that whole body clearance of thyroxine (T4) is increased in hyperthyroid rats isotopically equilibrated with radioactive T4, using the 24 h post-injection serum T4 concentration in the clearance calculation. Data from this laboratory indicate that serum T4 concentration is lowest at this point yielding falsely high clearance values, particularly when high doses of T4 are injected. To investigate this problem further, two types of experiments were performed. First, rats were equilibrated with [125I]T4, 5 or 20 μg/day, and the urinary clearance of iodide derived from T4 (deiodinative clearance) was measured from 0–7 and 7–24 h after a T4 injection, using the T4 concentration in serum obtained at the midpoint of each urine collection period. Urine was then collected from the ureters for several 1 h periods during the 4th to 8th h following T4 injection, calculating clearances using the midpoint plasma T4 concentration. Second, normal rats were given a single dose of [125I]T4, 5 or 55 μg/rat, and deiodinative clearance was determined during the subsequent 0–7 and 7–24 h periods. The first experiment indicated that deiodinative clearance was significantly enhanced in rats equilibrated with the large dose of T4 under all conditions studied. In contrast, the clearance in normal rats given a single large dose of T4 was not significantly different from that of normal rats given a small dose of T4. These results support the view that T4 clearance is increased in hyperthyroidism, due in part to an increase in the deiodination of T4.
OOCYTE MATURATION AND GLYCOLYSIS IN ISOLATED PRE-OVULATORY FOLLICLES OF PMS-INJECTED IMMATURE RATS
Authors: Hillensjö Torbjörn
Published: December 2008

Graafian follicles were isolated by microdissection from the ovaries of PMS-injected immature rats killed at specific times on the day before ovulation. They were incubated in Krebs bicarbonate buffer containing 5 mm glucose and 1 % bovine serum albumin. The oocytes were recovered after incubation and examined by Nomarski interference contrast microscopy. The amount of lactate and glucose in the incubation medium was analysed enzymatically.

Oocytes recovered from follicles extirpated in the morning, i. e. before the endogenous LH surge, and incubated for 2–10 h were in the dictyate stage, while addition of LH or FSH to the medium resulted in oocyte maturation as revealed by germinal vesicle breakdown (GVB) and polar body formation. The time-course of GVB in vitro was similar to that seen in vivo after exogenous LH. Both gonadotrophins markedly enhanced lactate accumulation in the medium and, as studied for LH, glucose uptake by the follicles. The effects of LH but not those of FSH, on GVB and lactate formation were prevented by the presence of an antiserum against the β-subunit of LH. The gonadotrophic effects on GVB could be mimicked by the addition of prostaglandin E2 to the medium.

When the follicles were extirpated in the late afternoon, i. e. after the LH surge, and incubated in hormone-free medium for 4 h the oocytes showed GVB in a progressively increasing proportion depending on the time of follicle extirpation. Lactate formation by this group of follicles was markedly enhanced compared to that of "morning" follicles, but it could be even more stimulated by in vitro exposure to LH. A preliminary series of experiments on the effect of phosphodiesterase inhibitors showed that theophylline and isobutylmethylxanthine at certain concentrations completely blocked the LH effect on GVB, whereas a newly developed compound, ICI 63.197, in itself induced GVB.
DIFFERENT EFFECTS OF EXOGENOUS CYCLIC ADENOSINE MONOPHOSPHATE AND ITS DIBUTYRYL DERIVATIVE ON PLASMA GROWTH HORMONE, GLUCOSE, INSULIN AND CORTISOL
Authors: Vanderschueren-Lodeweyckx M. , Proesmans W. , Eggermont E. , Eeckels R.
Published: December 2008

The effects of the infusion in four different dosages (0.001, 0.005, 0.02 and 0.2 mg/kg/min during 60 min) of cyclic 3′,5′-adenosine monophosphate and of its dibutyryl derivative on plasma growth hormone and on glucose, immunoreactive insulin and cortisol were studied in 38 normal subjects and in 10 patients with idiopathic hypopituitarism. In normal subjects cyclic 3′,5′-adenosine monophosphate provokes an increase in plasma growth hormone levels (only when a dosage of 0.2 mg/kg/min is used) without any changes in plasma glucose, insulin and cortisol. The maximal value of the means is observed 75 min after starting the infusion. Dibutyryl cyclic 3′,5′-adenosine monophosphate (0.2 and 0.02 mg/kg/min) provokes a dose-related rise in plasma growth hormone levels which is always preceded by hyperglycaemia and hyperinsulinaemia. The peak of the mean growth hormone levels occurs at 135 min after initiation of the infusion. In all but one hypopituitary patients the nucleotides do not promote growth hormone secretion.

It is concluded that exogenous cyclic 3′,5′-adenosine monophosphate and its dibutyryl derivative may not be considered as analogous and that both compounds may contribute to study growth hormone release in normal subjects and in patients with growth abnormalities.
OOCYTIC MEIOSIS IN CULTURED RAT FOLLICLES DURING INHIBITION OF STEROIDOGENESIS
Authors: Lieberman M. E. , Tsafriri A. , Bauminger S. , Collins W. P. , Ahrén K. , Lindner H. R.
Published: December 2008

Steroid release by cultured Graafian follicles explanted from rat ovaries on the morning of pro-oestrus was measured by radioimmunoassay. Addition of cyanoketone (10−4m) or aminoglutethimide (10−3m) to the medium reduced the basal level of steroid secretion (progesterone, androstenedione and oestradiol-17β) and abolished the steroidogenic effects of luteinizing hormone (LH; 5μg/ml) and prostaglandin E2 (PGE2; 10 μg/ml). However, the induction of oocyte maturation by either LH or PGE2 was not impaired by total suppression of the steroidogenic response of the follicles to these hormones by cyanoketone or aminoglutethimide. It is concluded that the meiosis-inducing action of LH on the mammalian egg is not mediated by the effect of the hormone on the rate and pattern of follicular steroidogenesis.
RISE IN DEHYDROEPIANDROSTERONE AND OESTROGENS DURING CLOMIPHENE ADMINISTRATION IN NORMAL MEN
Authors: Kampmann J. P. , Jørgensen F. Schønau , Bennett E. P. , Johnsen Svend G.
Published: December 2008

Serum concentrations of LH, FSH and testosterone, and urinary excretion of individual 17-ketosteroids, oestrogenic substances and free cortisol was investigated in 12 normal men after a daily administration of 50 mg clomiphene citrate for 14 days. A significant increase in the serum concentrations of LH, FSH and testosterone was seen after 8 days with a further increase when measured a week later. The percentual increase in urinary excretion of oestrogens and dehydroepiandrosterone was of the same order as the increase in serum testosterone concentration whereas the increase in androsterone and a aetiocholanolone was significantly lower. The excretion of free cortisol was unaltered. The study indicates that measurements of oestrogens in the urine might be used as a parameter of the stimulatory effect of clomiphene on the hypothalamic - pituitary - gonadal axis in man. In addition, the results support the hypothesis of an independent effect of clomiphene on adrenal steroidogenesis, not related to the production of glucocorticoids.
ACTION OF KI, THYROXINE AND CYCLIC AMP ON [3H]URIDINE INCORPORATION INTO THE RNA OF THYROID SLICES
Authors: Pisarev Mario A. , Aiello Leonardo O. , de Pisarev Diana L. Kleiman
Published: December 2008

Potassium iodide (KI) has been shown to impair thyroid protein biosynthesis both in vivo and in vitro. The present study was performed in order to clarify its mechanism of action. Ribonucleic acid (RNA) synthesis was studied in beef thyroid slices with either [32P] or [3H]-uridine as labelled precursors. Both KI and thyroxine (T4) at 10−5 m significantly decreased RNA labelling under our conditions. In other experiments RNA degradation was examined in pulse-labelled and actinomycin D-treated slices. KI did not modify the degradation of the [3H]-RNA thus indicating that it interferes with the biosynthesis rather than with the degradation of RNA. Taking the perchloric acid soluble radioactivity as a rough index of the precursor pool the present results would indicate an action at this level.

Both KClO4 and methylmercapto-imidazole relieved the gland from the inhibitory action of KI, supporting the view that an intracellular and organified form of iodine is responsible for this action. Since T4 also reproduced the effects of KI on RNA synthesis we would like to propose iodothyronines as the intermediates of this action. Cyclic AMP has been shown to stimulate thyroid protein biosynthesis. The present results demonstrate an action at the RNA level. Cyclic AMP increased both the PCA-soluble and RNA-linked radioactivity, thus suggesting an effect at the RNA precursor pool. KI at 10−5 m blocked the action of 2 mm cyclic AMP.
ACQUIRED RESISTANCE TO PARATHYROID HORMONE
Authors: Sinha Tushar K. , Queener Sherry F. , Bell Norman H. , Larson Sarah
Published: December 2008

Studies are presented in a patient with pseudohypoparathyroidism who showed a partial response to parathyroid extract. Resistance to the extract was observed after its short-term administration for the fourth time. Serum from the patient contained antibodies of the γG globulin class which bound 125I-labelled bovine parathyroid hormone. Prior incubation of parathyroid hormone with the serum prevented the activation in vitro of adenylate cyclase from pork renal cortex. The antibodies were directed primarily toward the C-terminal portion of the molecule. Thus, clinical resistance to parathyroid hormone is attributed to specific antibodies.
THE INSULIN TOLERANCE TEST AFTER PRE-TREATMENT WITH DEXAMETHASONE
Authors: Osterman P. O. , Wide L.
Published: December 2008

The plasma 11-hydroxycorticosteroid and serum GH responses to insulin-induced hypoglycaemia were studied in 25 healthy volunteers. The results of a control insulin tolerance test were compared with those of 2 similar tests which were performed after pre-treatment with dexamethasone 0.5 and 1.0 mg, respectively. The GH response to hypoglycaemia was significantly lower in women than in men in all 3 tests. In men, but not in women, the GH response was lower after pre-treatment with 1 mg dexamethasone than in the other 2 tests. The plasma 11-hydroxycorticosteroid response was significantly greater after pre-treatment with 0.5 mg dexamethasone than in the control test, and was at least as good after 1 mg dexamethasone. After pre-treatment with dexamethasone the subjects experienced less discomfort and a shorter duration of sweating than in the control insulin tolerance test. Pre-treatment with 1 mg dexamethasone also has other advantages. Thus, the basal plasma cortisol level is low and stable, which facilitates estimation of the magnitude of the cortisol response. Furthermore, information is obtained about the dexamethasone suppression response.
TRH-DEGRADING ENZYME ACTIVITY IN PERIPHERAL AND PITUITARY-PORTAL PLASMA OF THE RAT
Authors: Knigge K. M. , Schock D. , Ching M.
Published: December 2008

The enzymatic degradation of TRH was measured in peripheral and pituitary-portal plasma. Enzyme activity in peripheral plasma was 3.20 pg/min/μg plasma protein; in pituitary-portal plasma the rate of degradation was only 0.83 pg/min/μg protein. After dialysis, which removed virtually all endogenous TRH and LHRH, enzyme activity in peripheral and portal plasma was 2.24 and 0.60 pg/min/μg respectively. These data suggest that portal plasma contains large concentrations of unidentified substances which are competitive inhibitors or substrates for the enzyme or that portal plasma contains less TRH-degrading enzyme.
BIOLOGICALLY ACTIVE LUTEINIZING HORMONE (LH) IN PLASMA
Authors: Romaní P. , Robertson D. M. , Diczfalusy E.
Published: December 2008

A recently described in vitro bioassay method for the measurement of biologically active LH (Van Damme et al. 1974) has been applied to the plasma of normally menstruating and post-menopausal women. The specificity of the procedure was established according to the following evidence:

1. Parallelism was observed between dose response curves obtained with serial dilutions of a standard LH preparation (HMG 2nd IRP) and plasma pools collected during the follicular phase, at the LH-peak, during the luteal phase and after menopause.

2. There was no evidence for the presence of any synergistic or antagonistic factor in the various plasma specimens. The assay design used to establish this consisted of assaying the standard and plasma pool separately and then together as a mixture followed by an asssessment of the difference (if any) in the potencies obtained. Strict additivity should yield a relative potency of 1.0. Plasma pools which were obtained every 2–3 days throughout the menstrual cycle were assayed using this design against the standard (HMG 2nd IRP) and against a mid-cycle plasma pool obtained at the time of the LH-peak. The latter was also assayed against partially purified plasma fractions obtained from a post-menopausal plasma pool after gel filtration and isoelectric focusing. With the exception of 3 assays, in which the estimates of relative potency were 0.91, 0.94 and 0.95, respectively, in 19 assays of additivity, the fiducial limits always included unity.

3. Non-detectable LH levels were found in the plasma or serum of either hypophysectomized or hypopituitary hypogonadal men or women treated with oestrogen/progestogen combined pills.

4. The presence of calf or human serum in the assay medium is an essential requirement for a valid comparison of standard and unknown preparations. In their absence, non-parallel dose response curves between plasma and standard were obtained.

The other established criteria of reliability (sensitivity and precision) were also examined. The method is sufficiently sensitive (3.5–8.0 mIU/ml plasma; HMG (2nd IRP) as standard) for the measurement of LH throughout the cycle. The mean index of precision (λ) in 230 multiple assays was 0.040.

It is concluded that the modified bioassay yields valid and reliable estimates of LH when applied to human plasma obtained throughout the menstrual cycle and after menopause.
TESTOSTERONE AND 5α-ANDROSTAN-17β-OL-3-ONE (DHT) LEVELS IN MAN
Authors: Vermeulen A.
Published: December 2008

In order to test the hypothesis that plasma 17β-hydroxy-5α-androstan-3-one (DHT) levels might represent a parameter of androgenicity independent of testosterone (T) levels, the T/DHT ratio was determined at low and high T levels in both sexes. High T levels in males were obtained either by stimulation of endogenous T secretion, by im injection of either short or long-acting T esters and finally by oral administration of 200 mg of crystalline testosterone. In females high T levels were obtained either by im injection of long-acting T esters or by oral administration of 200 mg of T.

It was observed that the T/DHT ratio was not a function of sex but a function of T levels, whether T had an endogenous or a exogenous origin. When, as in patients with porto-caval shunt or cirrhosis of the liver, the liver was bypassed, oral administration of T resulted in relatively higher DHT levels than expected from T levels: this suggests an extra-hepatic origin of plasma DHT and/or a decreased hepatic metabolism of DHT. In a patient with the testicular feminization syndrome the T/DHT ratios both under basal conditions and after im injection of T propionate were similar to those observed in normal subjects.
PITUITARY HORMONE RESPONSES TO HYPOTHALAMIC RELEASING HORMONES IN ACROMEGALY
Authors: Cantalamessa L. , Reschini E. , Catania A. , Giustina G.
Published: December 2008

The pituitary reserve of GH, prolactin, TSH, LH, and FSH has been studied in a group of 13 acromegalic patients with the aim of evaluating the pituitary function and the activity of the disease. Plasma GH, TSH and prolactin were determined after thyrotrophin releasing hormone (TRH) administration, plasma gonadotrophins and GH after luteinizing hormone releasing hormone (LH-RH) administration.

The plasma TSH response to TRH was generally blunted in the patients treated with pituitary irradiation; however, none of the patients with diminished TSH reserve had signs of hypothyroidism. Six acromegalics showed prolactin basal levels higher than controls; none had galactorrhoea; 4 of them complained of impairment of the gonadal function. The prolactin response to TRH was variable and not related to prolactin basal levels. A subnormal LH reserve after LH-RH stimulation was observed in 5 out of 10 patients; 4 of them had also clinical signs of hypogonadism. A normal FSH response to LH-RH was present in all patients.

A non-specific GH response to TRH and/or LH-RH was obtained in about half of the acromegalics studied. The GH responsiveness to TRH and/or LH-RH was not related to the activity of the disease or to a specific derangement of the hypothalamo-pituitary function. A concordant response was observed only between GH and prolactin response to TRH; the highest prolactin responses to TRH were obtained in the GH responsive patients. Each patient showed a constant GH pattern of response on repeated testing. Even after pituitary irradiation the pattern of GH response was unchanged in spite of lowered GH plasma levels.
THE FIRST INTERNATIONAL STANDARD FOR HUMAN URINARY FSH AND FOR HUMAN URINARY LH (ICSH), FOR BIOASSAY
Authors: Storring P. L. , Dixon H. , Bangham D. R.
Published: December 2008

This paper describes the preparation and nature of the First International Standard for Human Urinary Follicle Stimulating Hormone and for Human Urinary Luteinizing Hormone, for Bioassay, and of two batches of working standard which were prepared from the same material.

A collaborative study of these materials was carried out by six laboratories in six different countries. The FSH and LH activities of the Standard were assayed in terms of those of the Second International Reference Preparation of Human Menopausal Gonadotrophins, Urinary, for Bioassay, which it replaces. The results from 20 valid FSH assays and 30 valid LH assays (using four different methods) obtained in this way gave a weighted combined potency estimate for FSH of 53.7 IU, with 95 fiducial limits of 47.2–61.1 IU, and for LH of 46.2 IU, with 95% fiducial limits of 43.3–49.3 IU. Accelerated degradation studies of the Standard stored at elevated temperatures suggested that the stability of both FSH and LH activities under normal storage conditions would be satisfactory. The FSH and LH activities of the two batches of working standard (WS-A and WS-B) were compared with those of the Standard and were not found to differ significantly, except for the LH activity of WS-B which appeared to be slightly higher than that of the Standard. Accelerated degradation studies did not show any significant differences in stability between the Standard and batches of working standards.

On the basis of these results the Standard has been established by WHO and allocated a potency for FSH of 54 IU per ampoule and for LH 46 IU per ampoule. The International Units for FSH, Human Urinary, for Bioassay and for LH (ICSH), Human Urinary, for Bioassay are thus defined as the activities contained in 0.11388 mg and 0.13369 mg of the International Standard, respectively.
EFFECT OF AGE AND SEX ON CIRCULATING AND PITUITARY PROLACTIN LEVELS IN HUMAN
Authors: Yamaji T. , Shimamoto K. , Ishibashi M. , Kosaka K. , Orimo H.
Published: December 2008

In an attempt to determine whether age or sex affects prolactin secretion in the human, basal levels of serum prolactin, and its response to TRH administration as well as the pituitary content of this hormone were compared between both sexes and among the different age groups. In 315 adult subjects of various ages, the mean basal levels of prolactin were found to be higher in women than in men of the same age groups with the exception of the sixth decade. The effect of age on serum prolactin concentrations, on the other hand, was not demonstrated. Similarly, the prolactin response to intravenous injections of 500 μg of TRH was significantly greater in female subjects than in males of both young and aged groups. No relationship between the prolactin response and the day of menstrual cycle in young women was apparent. Although quantitative difference in TRH-induced prolactin release was not observed between young and elderly subjects, the occurrence of prolactin peak and the elimination of the circulating prolactin following TRH administration were delayed in the aged groups. Taken together with the demonstration of a higher content of this hormone in female pituitary glands compared with those of males, it was concluded that prolactin secretion is enhanced in female subjects throughout life after puberty and that aging, per se, is not associated with an alteration in the rate of secretion of this hormone in human subjects.
THE EFFECT OF ATROPINE ON THE INSULIN RELEASE CAUSED BY ORAL AND INTRAVENOUS GLUCOSE IN HUMAN SUBJECTS
Authors: Henderson J. R. , Jefferys D. B. , Jones R. H. , Stanley D.
Published: December 2008

Oral and intravenous glucose tolerance tests were performed on normal fasting subjects, with and without atropine. Insulin release after oral glucose was significantly diminished by atropine, and this effect could not be ascribed to the drug delaying glucose absorption. However, insulin release brought about by intravenous glucose was not altered by atropine. Possible interpretations of these results are discussed.
SERUM THYROTROPHIN, PROLACTIN AND GROWTH HORMONE, RESPONSE TO TRH DURING OESTROGEN TREATMENT
Authors: Rutlin E. , Haug E. , Torjesen P. A.
Published: December 2008

The serum levels of thyrotrophin (TSH), prolactin (PRL) and growth hormone (GH) and the response of these hormones to 500 μg thyrotrophin-releasing hormone (TRH) iv were studied in menstruating women. in post-menopausal women before and after 2 mg oestradiol valerate for 5 consecutive days, and in men on long term oestrogen treatment. Oestrogen treatment had no effect on basal serum TSH levels, which were within the normal range in all groups. The TSH response to TRH was not different in menstruating and post-menopausal women and was not changed in the latter group after oestrogen treatment. In men treated chronically with oestrogens, the TSH response to TRH was similar to that found in normal male subjects.

There was no difference in basal levels of serum PRL between males and menstruating females. In the post-menopausal women, however, basal levels of serum PRL was significantly decreased, but rose during oestrogen treatment to serum levels normally found in menstruating women. In the oestrogen treated males basal serum PRL levels were significantly higher than in untreated men. The PRL response to TRH was significantly greater in females than in males, but in the oestrogen treated males the PRL response to TRH was greatly increased and almost of the same magnitude as the response in females. There was no difference in PRL response between menstruating and post-menopausal women, and oestrogen treatment of the latter group had no significant effect on the PRL response.

Basal levels of serum GH did not differ between the groups. In the group of 9 post-menopausal women one subject showed a small GH response to TRH prior to oestrogen treatment, while 7 subjects showed GH responses to TRH after oestrogen treatment. In the group of 5 chronically oestrogen treated men, 2 subjects had increased serum levels of GH after TRH.

Thus our data show that oestrogen administration may induce PRL release in human subjects, while oestrogens seem to play a far less important role in the regulation of GH and TSH secretion.
CHANGES IN THE CONCENTRATIONS OF ALDOSTERONE IN THE PLASMA AND ADRENAL GLANDS OF THE FOETUS, THE NEWBORN AND THE PREGNANT GUINEA-PIG DURING THE PERINATAL PERIOD
Authors: Giry J. , Delost P.
Published: December 2008

Plasma and adrenal aldosterone concentrations have been estimated by radioimmunoassay and by gas phase chromatography in the foetus, the newborn and the mother between day 62 of pregnancy and day 8 of post-natal life. The pre-natal period is characterized by a gradual increase in plasma and adrenal aldosterone levels from day 62 up to 67. Birth greatly stimulates the synthesis and the release of aldosterone. In the neonatal period there are two peaks of maximum intensity in the plasma aldosterone concentration, one at 12 h together with a high adrenal aldosterone level, the other on day 5. In the mother the plasma aldosterone concentration is always higher than that of the foetus during the pre-natal period and increases from day 64 of gestation until parturition and remains high during the first 24 h after parturition.
METABOLISM OF NORGESTREL BY THE HUMAN ENDOMETRIUM AND MYOMETRIUM IN VITRO
Authors: Uniyal J. P. , Buckshee K. , Hingorani V. , Laumas K. R.
Published: December 2008

Under in vitro conditions, the human endometrium and myometrium metabolized norgestrel to 13β-ethyl,17α-ethynyl-5β-oestrane,3α,17β-diol; 13β-ethyl,17α-ethynyl-5β-oestrane,3β,17β-diol and to some unidentified polar compounds, which suggests that the enzyme 3-ketosteroid reductase is present in these tissues. There was no qualitative difference in the conversion of norgestrel to its metabolites by the endometrium and myometrium, though some quantitative differences were observed i.e. more norgestrel was metabolized by the proliferative as compared with the secretory endometrium and myometrium. Furthermore, the conversion of norgestrel to its metabolites was higher in the endometrium as compared with the myometrium. Among the subcellular fractions of the endometrium and myometrium, the cytosol fraction showed the highest conversion of norgestrel. The main metabolite formed in the endometrium, myometrium and in their subcellular fractions was 3α-hydroxy-5βH-tetrahydronorgestrel. The implications of the formation of metabolites of norgestrel with very low biological activity as a factor involved in the regulation of the action of norgestrel in the endometrium are discussed.
CORTICOSTERONE BINDING BY MOUSE SERA DURING FOETAL AND POST-NATAL DEVELOPMENT
Authors: Savu Lia , Nunez Emmanuel , Jayle Max-Fernand
Published: December 2008

The binding properties of corticosterone binding globulin (CBG) of mouse sera have been studied by equilibrium dialysis and electrophoretic techniques, at different stages of foetal and post-natal development.

Scatchard analysis has demonstrated in all cases a single class of high affinity saturable binding sites for corticosterone. Remarkable increases of the binding capacities were observed in the foetal and pregnant sera, as compared to normal adult and immature levels. The mean values of n1M1 × g−1 of serum proteins (concentration of binding sites, n1 × moles of binding proteins M1) were 21 10−8 in 14–19 day pregnant females, 17 10−8 in the amniotic fluid, 4.2 10−8 in 14–19 day embryos, and only 0.8 10−8 in the normal adult female. Neonatal mice, aged 0–6 days exhibited no CBG activities. The association constants showed values of 2.5–4.1 108 m−1 when measured with foetal sera, and of 1.2–2.1 108 m−1 with pregnant or control adult sera and with the amniotic fluid, at 25°C. Comparative electrophoretic, thermal denaturation and competition studies with foetal and pregnant plasma CBG's are also reported.

The results are discussed in relation to the origin of CBG in the foetal serum, and also with respect to similar studies in the rat, guinea pig and man. The possible biological implications of serum steroid binding proteins in mammalian development are briefly outlined.
EFFECT OF INCREASED IODIDE INTAKE ON THYROID FUNCTION IN SUBJECTS ON CHRONIC LITHIUM THERAPY
Authors: Spaulding S. W. , Burrow G. N. , Ramey J. N. , Donabedian R. K.
Published: December 2008

Thyroid function tests were obtained in 10 patients on chronic lithium therapy before and after the administration of potassium iodide 250 mg q. i. d. Mean serum TSH rose by 8.9 μU/ml and mean serum T3 rose from 70 to 101 ng/dl. Two patients became hypothyroid; a third showed a rise in TSH without any change in T3 or T4. A fourth patient developed hyperthyroidism probably secondary to the Jod-Basedow phenomenon. Pharmacologic doses of iodine should be administered with caution to patients on chronic lithium therapy.
ANTI-OESTROGEN ACTION: UTERINE NUCLEAR RETENTION OF THE CI-628 ANTI-OESTROGEN RECEPTOR COMPLEX IN VITRO
Authors: Rinehart John S. , Ruh Thomas S. , Ruh Mary F.
Published: December 2008

Experiments were performed in vitro which compared the nuclear retention of the anti-oestrogen receptor complex formed by CI-628 and the nuclear retention of the oestrogen receptor complex formed by oestradiol-17β. Uterine nuclei retained the CI-628 receptor complex regardless of whether uterine incubations were carried out in the continued presence of CI-628 or whether, after 1 h, uterine incubations were continued in fresh medium. However, for oestradiol-17β there was a rapid decrease in the amount of receptor complex retained in the nucleus with time. When extractions using KCl were performed on nuclei after maximal accumulation of receptor complex by oestradiol-17β or CI-628, the oestrogen receptor complex was found to have a higher relative nuclear affinity than did the CI-628 receptor complex. These studies suggest different nuclear binding sites for these complexes.
FSH: II. EVIDENCE FOR ITS MEDIATING ROLE ON TESTOSTERONE SECRETION IN HYPOPITUITARISM
Authors: Sizonenko Pierre C. , Rappaport Raphael , Josso Nathalie , Dray Fernand
Published: December 2008

Testicular responses to administration of human chorionic gonadotrophin (HCG) in 23 hypopituitary patients were compared to responses obtained in adequate control groups and correlated to basal plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels. Sixteen nonpubertal patients demonstrated a significantly diminished testosterone response (250 ± 64 ng/100 ml, mean ± sem) along with low basal plasma FSH values (1.4 ± 0.2 mU/ml) when compared to normal response (607 ± 97 ng/100 ml) and normal FSH level (2.3 ± 0.2 mU/ml), but with normal LH values. In 7 pubertal patients decreased testosterone responses to HCG (815 ± 147 ng/100 ml) were observed with normal plasma FSH and LH values. Correlation between testosterone responses and FSH levels (r = 0.718, P < 0.002) in the pre-pubertal hypopituitary patients was highly significant. No such correlation was observed between testosterone response and LH. The present findings may a) give one explanation for the absence of response to HCG observed in some cases of hypo-pituitarism, b) give support to the hypothesis that FSH has a mediating role on LH-induced secretion of testosterone by the testis in human subjects.
EFFECT OF ADMINISTRATION FREQUENCY OF GROWTH HORMONE ON LONGITUDINAL BONE GROWTH IN THE HYPOPHYSECTOMIZED RAT
Authors: Thorngren K.-G. , Hansson L. I.
Published: December 2008

The effect of the administration frequency of growth hormone on longitudinal bone growth was investigated with tetracycline as intravital marker of the bone growth of the proximal tibia in hypophysectomized rats.

The total dose of growth hormone (NIH-GH-B16) and the administration period were the same in all compared experiments. It was possible to achieve an optimum growth response for a certain total dose of growth hormone by increasing the injection frequency. The period of hormone administration was 10 or 5 days followed by a 10 days withdrawal period. When the growth hormone was administered alone or in association with L-thyroxine for 10 days, the optimum injection frequency for growth hormone was found to be 1 inj./day in hypophysectomized rats and 2 inj./day in thyroxine-treated hypophysectomized rats.

When the administration period was 5 days for growth hormone given in association with L-thyroxine, the growth stimulation induced by one daily growth hormone injection was the same as that induced by two or four daily injections of the same total dose.

An increase in the administration frequency for a total daily dose of thyroxine from 1 to 2 inj./day did not increase the longitudinal bone growth either when thyroxine was given alone or in association with growth hormone.
THE EFFECT OF TREATMENT OF HYPERAND HYPOTHYROIDISM ON URINARY EXCRETION OF CYCLIC ADENOSINE 3′,5′-MONOPHOSPHATE
Authors: Carter D. J. , Heath D. A.
Published: December 2008

The urinary excretion of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) was examined in patients with hyperthyroidism and primary hypothyroidism, before treatment and at least six months later on return to euthyroid status.

Urinary cyclic AMP excretion was significantly greater in the hyperthyroid group than in the hypothyroid group both in the basal state (P < 0.01) and the ambulant state (P < 0.001).

In ambulant hyperthyroid patients absolute urinary cyclic AMP excretion (μmol/24 h) was significantly greater (P < 0.05) prior to treatment than on return to euthyroid status. In the hypothyroid group no significant change occurred after treatment with 1-thyroxine (P > 0.05).

The mechanism of changes in urinary cyclic AMP excretion in thyroid disease are discussed.
STUDIES OF A THYROID HORMONE AND ANDROGEN DEPENDENT PROTEIN IN RAT LIVER CYTOSOL
Authors: Dillmann Wolfgang H. , Silva Enrique , Surks Martin I. , Oppenheimer Jack H.
Published: December 2008

Sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis of the liver cytosol of euthyroid male rats revealed a prominent band (molecular weight, 26 000 daltons), designated Protein II, which was virtually absent in the cytosol of hypothyroid animals. Injection of 500 μg triiodothyronine (T3) per 100 g body weight resulted in a maximal increase in the level of Protein II, reaching 90% of the euthyroidal level 3 days after hormone administration. Concomitant studies with the liver mitochondrial enzyme alpha-glycerophosphate dehydrogenase (α-GPD) indicated that this T3 dose also resulted in a maximal enzyme response in this time period. Since we have estimated that 500 μg of T3 will saturate nearly all nuclear T3 binding sites, these results support the concept that the synthesis of both proteins is limited by nuclear binding. Protein II was absent in the liver cytosol of female rats but could be induced in ovariectomized female rats by androgens. Treatment of male rats with oestradiol resulted in disappearance of Protein II. Since administration of testosterone to hypothyroid male rats caused only a minimal increase in the amount of Protein II, the absence of the protein in hypothyroid animals was not due to androgen deficiency. Similarities in the molecular weight and the response to hormonal manipulation of Protein II and of the urinary α2uglobulin, previously reported by Roy (1973) raise the possibility that these proteins are the same. The high concentration of Protein II in male rat cytosol and the relative ease in its identification by SDS polyacrylamide gel electrophoresis make it a potentially useful model protein for the study of thyroid hormone action at the cellular level.
FAMILIAL ADRENOCORTICAL HYPOPLASIA WITH EARLY CLINICAL AND BIOCHEMICAL SIGNS OF MINERALOCORTICOID DEFICIENCY (HYPOALDOSTERONISM)
Authors: Petersen Knud E. , Tygstrup Inge , Thamdrup Erik
Published: December 2008

Biochemical investigations in a boy with a salt losing syndrome revealed a very low secretion of aldosterone which did not rise during salt deprivation, in spite of a normal rise in plasma renin activity. Cortisol secretion was normal - but subsequently decreased, while the corticosterone secretion was high. The patient was studied at the age of 5 weeks, 3 months and also at the age of 8 months. He survived until the age of 18 months on treatment with sodium chloride and DOCA, but did not receive glucocorticoids. At autopsy the adrenal glands were absent, but in fat tissue from the upper renal poles foetal adrenal cortex tissue was found. The histological picture agrees well with other cases which could be designated as "foetal-cortex-only" adrenal hypoplasia. The same histological changes were demonstrated in the boy's brother who died suddenly at the age of 6 weeks.

The boy's testes were advanced in maturation to a stage of about ten years: spermatocytes and Leydig cells were present.
STABILIZATION AND ASSAY OF A 17β-HYDROXYSTEROID DEHYDROGENASE IN THE SERUM OF PREGNANT WOMEN
Authors: Lübbert H.
Published: December 2008

Up to the present the activity of the 17β-hydroxysteroid dehydrogenase (17β-HSD) in the blood of pregnant women has not been accurately measured because of its great instability.

The enzyme was stabilized by mixing fresh serum with an equal volume of potassium phosphate buffer (100 mm, pH 7.4), containing 40 % (v/v) glycerol, 40 μm oestradiol-17β (Oe2) and 0.4 % (v/v) ethanol. Under these conditions the 17β-HSD was stable for several days at −20, +4 and 20°C and resistant to heat denaturation at 60°C.

The Km-value for Oe2 with NAD or NADP as cosubstrate was 5 × 10−6 or 2 × 10−6 M, respectively. In the presence of NAD, Oe2 was oxidized twice as rapidly as with NADP. The Km-value for NAD was 10−5 m.

Under the conditions of assay [3H]oestrone formation was linear with time (3 h) and with protein concentration.

Serum enzyme activities in normal pregnancies (between 20 and 60 μU/ml serum at the end of gestation) were nearly twice as high as those reported by other investigators. In normal single and twin births highest activities were obtained at the expulsion of the placenta which in all cases was followed by a rapid decrease in activity.
EVOLUTION OF THE MENSTRUAL PATTERN OF GONADOTROPHIN AND SEX STEROID CONCENTRATIONS IN SERUM
Authors: Penny Robert , Parlow Albert F. , Olambiwonnu N. Olantunji , Frasier S. Douglas
Published: December 2008

Consecutive daily serum samples were obtained over 25–30 days from 2 pre-pubertal girls (Stage I), 2 girls with breast development alone (Stage II); one girl with both breast development and pubic hair (Stage III), and 2 girls who were six months and three years post-menarche, respectively (Stage IV). All serum samples were assayed for LH, FSH, progesterone and 17-hydroxyprogesterone. Sera from 6 girls were assayed for testosterone, and sera from 3 were assayed for oestradiol.

The patterns of gonadotrophins and sex steroid concentrations in both Stage I and Stage II girls were characterized by day to day stability. LH and FSH concentration was increased in Stage II subjects, while steroid concentration were similar to those in Stage I. The Stage III subject showed marked, apparently random, fluctuations in the concentrations of LH, FSH, oestradiol and 17-hydroxyprogesterone. In Stage IV, as early as six months post-menarche, there was a definite peak in the serum concentration of gonadotrophins, 17-hydroxyprogesterone and oestradiol. However, luteal phase length and maximal progesterone levels of these post-menarchial girls were less than those observed for normal adult females.

These data are consistent with evolution of the adult menstrual pattern of hormone secretion through a series of developmental stages.