bluuebunny/crossref_metadata_2025 huggingface dataset:
ABILITY OF MOLAR TROPHOBLASTS TO SPLIT THE SIDE-CHAIN OF [26-14C]CHOLESTEROL IN VITRO
Authors: GUNASEGARAM R. , PEH K. L. , CHEW P. C. T. , KARIM S. M. M. , RATNAM S. S.
Published: December 2008

University Department of Obstetrics and Gynaecology, Kandang Kerbau Hospital for Women, Singapore 8, Republic of Singapore

(Revised manuscript received 1 September 1978)

Evidence from various laboratories indicates that molar trophoblasts may be biosynthetically very active in vitro and capable of bringing about several steroidal transformations (Van Leusden & Siemerink, 1969; Coutts & MacNaughton, 1971). However, a lack of incorporation of labelled acetate into pregnenolone and progesterone by molar vesicles has been observed by Van Leusden (1971) and Van Leusden & Villee (1966). Van Leusden (1971) also failed to demonstrate the conversion of [5-3H]mevalonate into sterols, cholesterol and steroids by these vesicles. These observations could be interpreted as indicating that the molar vesicles lack or possess only a very limited capacity to biosynthesize cholesterol from acetate and mevalonate. There also remains the distinct possibility that the vesicles are deficient in the C-20,22-desmolase complex that cleaves the sterol molecule into pregnenolone and
DIVALENT CATIONS AND ANGIOTENSIN-STIMULATED SODIUM TRANSPORT
Authors: MUNDAY K. A. , PARSONS B. J. , POAT JUDITH A. , SMITH D. J.
Published: December 2008

The presence of calcium in the fluid in which intestinal or kidney tissue is incubated is required for the tissue to respond to angiotensin. Everted sacs of rat colonic mucosa exhibited an increased rate of fluid transport in the presence of angiotensin; this response was lost when the serosal fluid, but not the mucosal fluid, was calcium-free. Angiotensin-stimulated transport was maintained when calcium was replaced with strontium or barium, but was lost when calcium was exchanged for magnesium. Similarly, calcium ions were required in the incubation fluid of rat kidney cortex slices to demonstrate angiotensin-enhanced sodium transport. These observations are discussed in relation to the possible roles of divalent cations in the mechanism of action of angiotensin.
INHIBITION OF ALDOSTERONE PRODUCTION IN ADRENAL CELL SUSPENSIONS BY SERUM FROM PATIENTS WITH MANIC-DEPRESSIVE PSYCHOSIS
Authors: O'BRIEN M. J. , LEVELL M. J. , HULLIN R. P.
Published: December 2008

A method of preparing a suspension of cells of the zona glomerulosa from rat adrenal capsules treated with crude collagenase is described. The cells responded to ACTH, angiotensin II and serotonin by increased production of aldosterone. Pooled human sera or individual human sera (from healthy normal or non-psychiatric in-patients) to a final concentration of 30% had no effect on ACTH-stimulated production of aldosterone. Many serum samples from five patients with manic-depressive psychosis, however, caused a reduction in aldosterone production; 65% of those samples taken during depression, 44% of the samples taken during manic episodes and 23% of the samples taken when the mood was normal. Sera from manic-depressive patients also reduced the production of aldosterone caused by angiotensin II or serotonin. This effect of serum from manic-depressives in vitro may be related to the abnormalities of aldosterone control in such patients.
METABOLISM OF EXOGENOUS HUMAN CHORIONIC GONADOTROPHIN IN MEN
Authors: SOWERS J. R. , PEKARY A. E. , HERSHMAN J. M. , KANTER M. , DISTEFANO J. J.
Published: December 2008

The immunoreactivity of a commercial preparation of human chorionic gonadotrophin (HCG) was determined in a homologous double antibody radioimmunoassay for HCG using antisera to the β-subunit of the hormone. The immunoreactivity of the commercial HCG was found to be 2·2 ± 0·3 (mean ± 2 s.d.) times the biological potency. Exclusion chromatography of the commercial HCG and then curve resolution of the elution profile derived from the radioimmunoassay revealed that on a molar basis, 21% of the immunoreactivity was attributable to β-HCG. The rate of clearance of this preparation of HCG from the plasma after intravenous administration was determined as a function of the dose administered to ten normal men (age 36–64 years). The doses ranged from 10 000 to 300 000 i.u. immunological potency. The rate of clearance decreased significantly (r = 0·574, P< 0·05) with increasing doses of HCG from a mean of 786 ml/h at the lowest dose to a mean of 298 ml/h at the highest dose. The renal clearance of administered HCG also decreased with increasing doses; the mean renal clearance of the 10 000 i.u. dose was 3·6 times the mean renal clearance after administration of 200 000 i.u. When the accumulated urinary HCG was expressed as a percentage of the dose administered, 14·1% of the 10 000 i.u. dose and 9·8% of the higher doses accumulated in the urine, suggesting that non-renal clearance increased with increasing dose.
RELATIVE ACTIVITY, PLASMA ELIMINATION AND TISSUE DEGRADATION OF SYNTHETIC LUTEINIZING HORMONE RELEASING HORMONE AND CERTAIN OF ITS ANALOGUES
Authors: SWIFT A. D. , CRIGHTON D. B.
Published: December 2008

The abilities of three nonapeptide analogues of synthetic luteinizing hormone releasing hormone (LH-RH) to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in anoestrous and cyclic ewes were examined, as were their elimination from the plasma in vivo and degradation by extracts of the hypothalamus, anterior pituitary gland, lung, kidney, liver and plasma in vitro. In all cases, comparisons were made with synthetic LH-RH.

When injected i.v. into mature ewes as a single dose, the potencies of the analogues were graded and Des Gly-NH210 LH-RH ethylamide was found to be the least potent. It was not possible to demonstrate any significant increase in the potency of this analogue over LH-RH, although a trend was apparent with each parameter examined. [d-Ser(But)6] Des Gly-NH210 LH-RH ethylamide had the greatest potency. There were no differences between the responses of anoestrous ewes and those of ewes treated on day 10 of the oestrous cycle. None of the analogues had a rate of elimination from the plasma different from that of LH-RH during either the first or the second components of the biphasic disappearance curve.

The incubation of LH-RH with tissue extracts showed that extracts of the hypothalamus and anterior pituitary gland degraded LH-RH to a similar extent. Both the hypothalamic and anterior pituitary gland extracts degraded more LH-RH than did lung extract, which in turn destroyed more LH-RH than did extracts of kidney or liver tissue. The degradative abilities of kidney and liver extracts did not differ from each other. Plasma failed to degrade LH-RH or the analogues. Although LH-RH was rapidly destroyed by hypothalamic extract in vitro, of the analogues, only Des Gly-NH210 LH-RH ethylamide was degraded. The anterior pituitary gland and kidney extracts failed to degrade [d-Ser6] Des Gly-NH210 LH-RH ethylamide and [d-Ser(But)6] Des Gly-NH210 LH-RH ethylamide as rapidly as LH-RH. Extracts of liver and lung were incapable of catabolizing any of the analogues.

There was an inverse correlation between the LH- and FSH-releasing potency of an analogue and its rate of degradation by anterior pituitary gland extract. The slower rates of catabolism of certain analogues of LH-RH by the anterior pituitary gland may explain their increased LH- and FSH-releasing potency.
IMMUNOLOGICAL PROPERTIES OF SYNTHETIC HUMAN PARATHYROID HORMONE 53–84 FRAGMENT
Authors: HENDY G. N. , MANNING R. M. , ROSENBLATT M. , TREGEAR G. W. , KEUTMANN H. T. , O'RIORDAN J. L. H.
Published: December 2008

The immunological properties of a synthetic peptide comprising the carboxyl-terminal 53–84 region of human parathyroid hormone (PTH) have been studied. The immunoreactivity of the synthetic human PTH-(53–84) peptide paralleled that of a 53–84 fragment of the native human hormone prepared by enzymic digestion, in both a standard radioimmunoassay, which was not region-specific, and also a radioimmunoassay specific for the carboxyl-terminal region of PTH. However, in both types of radioimmunoassay the synthetic human PTH-(53–84) peptide was four to five times more reactive than the native human PTH-(53–84) fragment.
INTERNATIONAL REFERENCE PREPARATION OF HUMAN PROLACTIN FOR IMMUNOASSAY: DEFINITION OF THE INTERNATIONAL UNIT, REPORT OF A COLLABORATIVE STUDY AND COMPARISON OF ESTIMATES OF HUMAN PROLACTIN MADE IN VARIOUS LABORATORIES
Authors: GAINES DAS ROSE E. , MARY COTES P.
Published: December 2008

As authorized by the World Health Organization 29th Expert Committee on Biological Standardization, the preparation of human prolactin in ampoules coded 75/504 has been established as the International Reference Preparation (IRP) of human prolactin for immunoassay. From the results of a collaborative study, to which 15 laboratories in nine countries contributed, with the agreement of the participants, the content of each ampoule is defined as 0·650 International Units (i.u.; 650 mi.u.) immunoassay. The results of this collaborative study show that the IRP is adequately stable and suitable for use as a standard for the determination of prolactin in human plasma and serum. Estimates of the prolactin content of human plasma and serum made in the various laboratories have been compared and show good agreement in ranking order, but only fair agreement in the numerical value of the estimates. Numerical agreement is poor between estimates of the human prolactin content of two samples identical except for coding; this shows the difficulty in achieving continuity of estimates when any laboratory calibrates a replacement standard.
MORPHOLOGICAL CHANGES IN THE ENDOCRINE PANCREAS IN PREGNANT RATS WITH EXPERIMENTAL DIABETES
Authors: VAN ASSCHE F. A. , AERTS L. , GEPTS W.
Published: December 2008

This present study has demonstrated that during normal pregnancy in the rat the number of β-cells is increased (hyperplasia) and the volume of the individual β-cells is increased (hypertrophy).

During experimental diabetes, however, the endocrine pancreas has an impaired capacity to compensate during pregnancy. In the experimental diabetic pregnant rat the β-cells cannot replicate due to the unfavourable metabolic environment. This could reflect the complications caused by diabetes during human pregnancy.
TRANSPORT OF THYROXINE IN THE SERUM OF VITAMIN A-DEFICIENT RATS
Authors: HIGUERET P. , GARCIN H.
Published: December 2008

Thyroxine (T4) transport in the serum of rats deficient in vitamin A was studied by electrophoresis after incubation of serum samples with radioactive T4. In serum from vitamin A-deficient rats, the amount of radioactivity bound to the prealbumin zone of the electrophoretograms decreased, whereas there was an increase in the amount of radioactivity bound to the albumin zone. The serum from vitamin A-deficient rats subsequently fed a normal diet (repletion experiment) had an electrophoretic pattern similar to that of normal rats. The serum fraction which bound radioactive T4 appeared in the prealbumin rather than the albumin zone. These results suggest that vitamin A deficiency causes an early change in the transport of thyroid hormones in the plasma and a new level of serum thyroxine which may be responsible for the biochemical and physiological changes which occur in vitamin A-deficient rats.
INVOLVEMENT OF PROSTAGLANDINS IN THE INHIBITION OF GROWTH HORMONE PRODUCTION IN CULTURED PITUITARY CELLS BY INSULIN
Authors: BETTERIDGE A. , WALLIS M.
Published: December 2008

The effect of insulin was tested on the rate of synthesis and release of growth hormone in cultured rat anterior pituitary cells. Concentrations of insulin between 10−9 and 10−7 mol/l (6–600 ng/ml or 0·15–15 mu./ml) inhibited synthesis of growth hormone; 10−8 mol insulin/1 was most effective. The effect was observed after a time-lag of at least 1 h. Insulin at concentrations between 3 × 10−9 mol/l and 3 × 10−7 mol/l also inhibited growth hormone secretion in 30 min incubations. The most effective insulin concentration in this case was 3 × 10−8 mol/l. Insulin (10−9–10−7 mol/l) also decreased the intracellular content of prostaglandins E and F. The effect was rapid, reaching a maximum after 30 min. Indomethacin, an inhibitor of prostaglandin synthetase, dramatically lowered the concentration of prostaglandins in the cells within 30 min; growth hormone synthesis was also decreased, but not until after 2 h of incubation. The results suggest that an initial response to insulin treatment is a lowering of intracellular levels of prostaglandins, which may then mediate a decrease in growth hormone synthesis, after a 1–2 h delay.
EFFECTS OF EXOGENOUS CORTISOL ON THE UPTAKE OF CORTICOSTEROIDS BY THE ISOLATED PERFUSED GUINEA-PIG MAMMARY GLAND
Authors: PETERS A. R. , MEPHAM T. B.
Published: December 2008

Assay of corticosteroids in the plasma of guinea-pigs showed that concentrations were higher in lactating than in non-lactating and male animals. In five isolated perfused mammary gland experiments in which corticosteroids were at concentrations of 1·3–3·0 μg/ml in the perfusate, equivalent to concentrations during lactation, the mean (±s.e.m.) uptake by the mammary gland was 900 ± 210 ng g−1 h−1. In five experiments in which the concentrations of corticosteroid in the perfusate were 190–580 ng/ml, the uptake by the mammary gland was significantly lower (316 ± 73 ng g−1 h−1; P < 0·05). For the ten experiments there was a significant correlation between the concentration of corticosteroid in the perfusate and uptake by the mammary gland (P < 0·05). No convincing evidence for a galactopoietic role of corticosteroids in the guinea-pig was obtained, although administration of cortisol significantly stimulated the uptake of glutamine by the perfused gland.
TESTOSTERONE 5α-REDUCTASE ACTIVITY AS RELATED TO PROLIFERATIVE STATUS IN MOUSE ACCESSORY SEX GLANDS
Authors: ALISON M. R. , WRIGHT N. A.
Published: December 2008

Testosterone 5α-reductase activity has been measured during the proliferative response of the seminal vesicle and coagulating gland of the castrated mouse after continuous treatment with testosterone. Daily subcutaneous injections were begun either 3 or 14 days after castration. At 3 days after castration, a pre-replicative period of 50–60 h occurred before the onset of DNA synthesis, and a continuous [3H]thymidine labelling procedure revealed that only a minority of epithelial cells were subsequently involved in the transitory proliferative response. At 14 days after castration, cells were able to prepare more quickly for DNA synthesis (20–30 h), and the subsequent proliferative response involved a higher proportion of the epithelial cells present.

At 14 days after castration, testosterone treatment resulted in the activity of the enzyme/ mg homogenate increasing fourfold in the seminal vesicle and tenfold in the coagulating gland, to values almost double those of control (intact animals. At 3 days after castration, testosterone treatment resulted in much slower increases in enzyme activity, and at the completion of day 5 of treatment, levels were close to control values. It is concluded that a relationship may exist between the initial increase in 5α-reductase activity and the duration of the pre-replicative period before DNA synthesis begins. Although testosterone and its resultant effects upon 5α-reductase activity are clearly implicated in the genesis of the proliferative response, the ultimate control of cell proliferation must be independent of androgenic hormones. When cell division was effectively curtailed at the completion of day 4 of testosterone treatment, abnormally high levels of enzyme activity were still present.
PROLONGED RELEASE BY DIOESTROUS RATS OF FOLLICLE-STIMULATING HORMONE DURING THE PERIOD OF OVULATION INDUCED BY LUTEINIZING HORMONE RELEASING HORMONE
Authors: SASAMOTO SHUJI , HARADA SHIGEO , TAYA KAZUYOSHI
Published: December 2008

When 1·0 μg luteinizing hormone releasing hormone (LH-RH) was given i.v. three times at 1 h intervals from 17.00 to 19.00 h on the day of dioestrus (day 0) to regular 4 day cyclic rats, premature ovulation was induced the next morning (day 1) with the number of ova present comparable to normal spontaneous ovulation. The next spontaneous ovulation occurred on the morning of day 5, 4 days after premature ovulation induced by LH-RH.

Plasma concentrations of FSH and LH showed transient rises and falls within 1 h of administration of LH-RH; concentrations of FSH in the plasma decreased from 20.00 h on day 0 but markedly increased again from 23.00 h on day 0 to 02.00 h on day 1 and these high levels persisted until 14.00 h on day 1, with only a small increase of plasma LH during this period. The duration of increased FSH release during premature ovulation induced by LH-RH treatment was 6 h longer than the FSH surge occurring after administration of HCG on day 0. Surges of gonadotrophin were absent on the afternoon of day 1 (the expected day of pro-oestrus) and the surges characteristic of pro-oestrus occurred on the afternoon of day 4 and ovulation followed the next morning. The pituitary content of FSH did not decrease despite persisting high plasma levels of FSH during premature ovulation induced by either LH-RH or HCG on day 0.

The changes in uterine weight indicated that the pattern of oestrogen secretion from the day of premature ovulation induced by LH-RH to the day of the next spontaneous ovulation was similar to that of the normal 4 day oestrous cycle. When 10 i.u. HCG were given on day 0, an increase in oestrogen secretion occurred on day 2, 1 day earlier than in the group given LH-RH on day 0. This advancement of oestrogen secretion was assumed to be responsible for the gonadotrophin surges on day 3.

Similar numbers of fully developed follicles were found by 17.00 h on day 2 after premature ovulation induced by either LH-RH or HCG, suggesting that the shorter surge of FSH during premature ovulation induced by HCG had no serious consequences on the initiation of follicular maturation for the succeeding oestrous cycle in these rats.

Administration of LH-RH on day 0 had no direct effect on the FSH surge during premature ovulation. Secretory changes in the ovary during ovulation may be responsible for this prolonged selective release of FSH.
PLASMA TESTOSTERONE LEVELS IN INTACT AND HEMICASTRATED GROWING COCKERELS
Authors: DRIOT F. J. M. , DE REVIERS M. , WILLIAMS J.
Published: December 2008

Changes in the levels of testosterone in plasma were measured by radioimmunoassay in blood samples taken at frequent intervals between 2 and 26 weeks of age from entire cockerels and cockerels hemicastrated before 2 weeks of age. In both groups the pattern of testosterone secretion could be divided into three clearly defined phases. In young birds, the levels of testosterone in plasma were low (0·3 ng/ml) but in the prepubertal period, at 11 weeks of age, they started to rise and continued to rise until 22 weeks of age when adult levels, which fluctuated between 2·5 and 3·5 ng/ml, were reached. In the immediate period after hemicastration, the concentration of testosterone decreased temporarily. From 11 weeks of age the levels of testosterone in the hemicastrated birds were approximately 75% of those in intact birds.

These results are discussed in relation to the compensatory testicular hypertrophy which occurs in growing cockerels hemicastrated at an early age.
MATURATION OF THE INHIBITORY FEEDBACK ACTION OF OESTROGEN ON FOLLICLE-STIMULATING HORMONE SECRETION IN THE IMMATURE FEMALE RAT: A ROLE FOR ALPHA-FOETOPROTEIN
Authors: MEIJS-ROELOFS H. M. A. , KRAMER P.
Published: December 2008

The maturation of the inhibitory feedback action of oestrogen on FSH secretion in the immature female rat was studied from 5 days of age until after the first ovulation. To study the role of the oestrogen binding alpha-foetoprotein (AFP) which is present in the blood of young animals, the effects of various doses of oestradiol and of the synthetic oestrogen R2858 (11β-methoxy-17-ethynyl-oestradiol), which is not bound by AFP, were compared in ovariectomized rats.

A rise in the serum concentration of FSH within 2 days of ovariectomy was first observed in rats ovariectomized at 8 days of age. Between 8 and 28 days of age the rise in FSH after ovariectomy could be prevented by oestrogen injections in such a way that the resulting FSH concentration amounted to 50% of that in ovariectomized control rats. This was achieved with a constant dose of 0·00015 μg R2858/100 g body weight, whereas the dose of oestradiol needed decreased from 0·05 to 0·01 μg/100 g body weight indicating an increased sensitivity to the feedback action of oestradiol. After day 28, sensitivity to the feedback action of both R2858 and oestradiol decreased progressively up to the time of the first ovulation.

In contrast to results at earlier ages, none of the doses of either oestrogen was capable of maintaining near-physiological concentrations of FSH after 20 days of age.

It is concluded that the apparent increase in sensitivity to the feedback action of oestradiol occurring before 28 days of age reflects the disappearance of AFP from the blood, whereas the subsequent decrease in sensitivity is independent of AFP. Moreover, it is concluded that up to about 20 days of age oestradiol could be, though not necessarily is, the sole ovarian factor involved in regulating FSH secretion, whereas at later ages additional steroids and/or factors must be involved.
DO HYPOTHALAMIC REGULATORY FACTORS OTHER THAN LUTEINIZING HORMONE RELEASING FACTOR EXERT A PRIMING EFFECT?
Authors: PICKERING A. J.-M. C. , FINK G.
Published: December 2008

Extracts of hypothalamic tissue were applied to pituitary tissue in vitro to see whether they could exert a priming effect on gonadotrophin, adrenocorticotrophin, thyrotrophin or prolactin secretion. A clear-cut priming effect was seen only for gonadotrophin secretion.
PLASMA CONCENTRATIONS OF LUTEINIZING HORMONE, FOLLICLE-STIMULATING HORMONE AND PROGESTERONE DURING THE BREEDING SEASON IN EWES IMMUNIZED AGAINST ANDROSTENEDIONE OR TESTOSTERONE
Authors: MARTENSZ N. D. , SCARAMUZZI R. J.
Published: December 2008

Levels of plasma LH, FSH and progesterone during the breeding season were measured by radioimmunoassay in control ewes and ewes actively immunized against androstenedione-11α-hemisuccinyl–bovine serum albumin or testosterone-3(O-carboxymethyl)oxime–bovine serum albumin. Immunization against androstenedione resulted in normal oestrous cycles with raised plasma LH and progesterone levels and a reduction in the concentration of FSH during the luteal phase. It is tentatively suggested that androstenedione, or its metabolites, could modify the oestrogenic control of LH secretion and facilitate the release of FSH in the ewe.

Immunization against testosterone prevented oestrus and resulted in markedly increased levels of LH without alteration of the FSH concentration. Since evidence of increased binding of oestradiol-17β was found in the ewes immunized against testosterone, these results cannot be attributed solely to a reduction in the biologically active fraction of testosterone.
PLASMA CONCENTRATIONS OF LUTEINIZING HORMONE AND FOLLICLE-STIMULATING HORMONE DURING ANOESTRUS IN EWES ACTIVELY IMMUNIZED AGAINST OESTRADIOL-17β, OESTRONE OR TESTOSTERONE
Authors: MARTENSZ N. D. , SCARAMUZZI R. J. , VAN LOOK P. F. A.
Published: December 2008

The concentrations of LH and FSH in jugular venous plasma were measured during anoestrus in control ewes and ewes actively immunized against 17β-oestradiol-6-(O-carboxymethyl)oxime–bovine serum albumin, oestrone-6-(O-carboxymethyl)oxime–bovine serum albumin or testosterone-3-(O-carboxymethyl)oxime–bovine serum albumin. During a 12 h sampling period, the basal level of LH and the frequency of LH pulses were significantly increased in all the immunized animals. The plasma FSH concentration was increased in two out of five oestradiol-immunized ewes and two out of three oestrone-immunized animals. The plasma FSH concentration in the testosterone-immunized animals was similar to the control values.

Significant titres of antibodies to oestradiol-17β were found in all the immunized animals. It is suggested that binding of oestradiol-17β in the circulation by antibodies reduced the negative feedback action normally exerted by this steroid on LH secretion and, to a lesser extent, on FSH secretion. However, since the oestradiol antibody titres in the testosterone-immunized and oestrone-immunized ewes were considerably lower than those found in the oestradiol-immunized animals, it is possible that testosterone and oestrone, perhaps by acting as prehormones, could influence the negative feedback control by oestradiol-17β of gonadotrophin secretion in the anoestrous ewe.
PROSTAGLANDIN E, THROMBOXANE B2 AND 6-OXO-PROSTAGLANDIN F1α IN AMNIOTIC FLUID AND MATERNAL PLASMA OF RHESUS MONKEYS (MACACA MULATTA) DURING THE LATTER THIRD OF GESTATION
Authors: ROBINSON J. S. , NATALE R. , CLOVER L. , MITCHELL M. D.
Published: December 2008

The concentrations of prostaglandin E (PGE), thromboxane B2 (TXB2) and 6-oxo-prostaglandin F1α (6-oxo-PGF1α) were measured by radioimmunoassay in serial samples of amniotic fluid and maternal peripheral plasma in the latter third of pregnancy in rhesus monkeys (Macaca mulatta). The samples were collected under ketamine-induced anaesthesia. The concentration of PGE was undetectable in amniotic fluid until a few days before delivery when a large increase was observed in three of the five animals. There were small increases of TXB2 and 6-oxo-PGF1α in amniotic fluid before delivery. In maternal plasma the concentrations of PGE, TXB2 and 6-oxo-PGF1α were generally higher and more variable than in amniotic fluid and did not increase with advancing gestation. It is suggested that increased production of primary prostaglandins occurs before, and is involved in, the onset of parturition in the rhesus monkey.
3′-DEOXYADENOSINE AND IMPLANTATION OF DELAYED BLASTOCYSTS IN MICE
Authors: FERNANDEZ-NOVAL A. , LEROY F.
Published: December 2008

Pregnant mice were ovariectomized 3 days after mating and pregnancy was maintained by progesterone treatment. Different regimens of intraperitoneal injections of 3′-deoxyadenosine were applied 3 days after ovariectomy. Repetition of the injections at 3 h intervals induced a significant rate of implantation by delayed blastocysts. Other types of treatment with 3′-deoxyadenosine as well as adenosine injections were found to be ineffective. Paradoxically, 3′-deoxyadenosine treatment had an adverse effect on the overall pregnancy rate found at autopsy.
HYPERALDOSTERONISM IN THE SODIUM-DEPLETED RAT: MODE OF ALDOSTERONE-STIMULATING ACTION OF FRUSEMIDE
Authors: SPÄT A. , TARJÁN ÉVA , TÓTH G.
Published: December 2008

The mechanism of diuretic-induced hyperaldosteronism was examined in dexamethasone-pretreated rats. The diuretic drug frusemide brought about a rapid increase in plasma renin activity and aldosterone concentration in serum. Half an hour after the administration of frusemide the mean concentration of aldosterone was 25 times higher than in vehicle-treated control animals. Administration of SQ 20,881, an inhibitor of angiotensin converting enzyme, prevented the adrenal response to frusemide. The response of aldosterone was completely blocked by indomethacin. This drug reduced renin release and probably also inhibited the effect on the adrenal glands of angiotensin, released in response to frusemide. Our results indicate that the effects of diuretics on the adrenal glomerulosa cells are mediated by the renin–angiotensin system also in the rat. Hyperaldosteronism is dependent on the maintenance of prostaglandin synthesis. ACTH has no essential role in this response.
INHIBITORY ACTION OF FOLLICULAR FLUID ON PROGESTERONE AND PROSTAGLANDIN SYNTHESIS IN BOVINE FOLLICLES
Authors: SHEMESH MORDECHAI
Published: December 2008

The present studies examined the inhibitory effect of mid-cycle and preovulatory bovine follicular fluid (bFF) on the secretion of progesterone and prostaglandin F2α (PGF2α) by bovine theca and granulosa cells cultured in tissue culture Medium 199. The inhibitory effect of bFF on the secretion of PGF2α by incubated and cultured hemipituitary glands of male rats was also studied. Addition of 5, 10 or 20% charcoal-extracted, mid-cycle bFF to the culture medium caused a twofold decrease in the accumulation of both progesterone and PGF2α by the cultured granulosa cells (P < 0·01). In contrast, when preovulatory bFF was used, there was no inhibitory effect on secretion of progesterone and PGF2α. The addition of 10% mid-cycle bFF to the culture medium caused a two- to fourfold decrease in the accumulation of both PGF2α and progesterone by the cultured theca (P < 0·008). However, in the presence of 1 μg LH/ml, the inhibitory effect of mid-cycle bFF on progesterone and PGF2α secretion was abolished. The secretion of PGF2α was significantly (P < 0·03) decreased in male rat hemipituitary glands after 5 h of incubation or 18 h of culture. These findings suggest that bFF from mid-cycle follicles inhibits prostaglandin synthetase as well as luteinization. The inhibition disappeared with bFF from preovulatory follicles.
DISTRIBUTION AND DEGRADATION OF TWO TRITIUM-LABELLED CORTICOTROPHIN ANALOGUES IN THE RAT
Authors: BENNETT H. P. J. , McMARTIN COLIN
Published: December 2008

The distribution and degradation of corticotrophin-(1–24)-tetracosapeptide specifically labelled with tritium at Tyr2, Phe7 or Tyr23 and [d-Ser1, Lys17, Lys18]-corticotrophin-(1–18)-octadecapeptide amide labelled at Tyr2 were studied at various times after intravenous injection into rats. By characterizing the radioactivity in plasma and various tissues, an overall picture of the metabolic handling of the two peptides emerged. The peptides left the circulation rapidly, entering mainly muscle and skin where they were extensively degraded. The d-Ser1-containing analogue was less rapidly degraded and intact peptide persisted in muscle and skin for up to 1 h. This peptide probably returned to the circulation giving rise to the sustained plasma levels observed after injection of the d-Ser1-substituted octadecapeptide but not after injection of the tetracosapeptide. Although initially the kidneys did not clear such large amounts of peptide as did muscle and skin they played an important role by continuously and, on the basis of existing evidence, irreversibly clearing the peptides and peptide fragments from the circulation and degrading them.
LARGE-SCALE PREPARATION OF HIGHLY PURIFIED PYROGEN-FREE HUMAN GROWTH HORMONE FOR CLINICAL USE
Authors: JONES R. LUMLEY , BENKER G. , SALACINSKI P. R. , LLOYD T. J. , LOWRY P. J.
Published: December 2008

A method is described for the large-scale isolation of highly purified human growth hormone for therapeutic use. The hormone was extracted from frozen pituitary glands under mildly alkaline conditions. Purification was effected by gel filtration and ion-exchange chromatography. The final product was pyrogen-free and had a potency of 2·5 i.u./mg measured by bioassay against the current international standard. The yield of growth hormone/gland was approximately 5 mg.
OESTROGENIC EFFECTS OF CATECHOL OESTROGENS ON SECRETION OF PROLACTIN BY THE PITUITARY GLAND AND SYNTHESIS OF DNA BY THE MAMMARY GLAND IN OVARIECTOMIZED RATS
Authors: YANAI REIKO , NAGASAWA HIROSHI
Published: December 2008

The effects of 2-hydroxyoestradiol-17β and 2-hydroxyoestriol (2OH-OE3) on levels of serum prolactin, DNA synthesis by the mammary gland and the weight of the uterus were examined in ovariectomized Sprague–Dawley rats.

2-Hydroxyoestradiol-17β had a potent oestrogenic activity in stimulating the secretion of prolactin by the pituitary gland, the synthesis of DNA by the mammary gland and in increasing the weight of the uterus. On the other hand, 2OH-OE3 increased the weight of the uterus only.
BLOOD LEVELS OF SYNTHETIC GLUCOCORTICOIDS AFTER ADMINISTRATION BY VARIOUS ROUTES
Authors: MIYACHI YUKITAKA , YOTSUMOTO HIDEKI , KANO TAKASHI , MIZUCHI AKIRA , MUTO TETSUICHIRO , YANAGIBASHI KAZUYUKI
Published: December 2008

Using reliable radioimmunoassay methods, the concentrations of prednisolone, prednisolone-hemisuccinate, betamethasone and betamethasone-17-benzoate were determined after administration by various routes. Serum prednisolone and betamethasone concentrations increased to peak levels 2 h after oral administration and then decreased gradually. The half-times of disappearance of prednisolone and betamethasone from blood, after a single oral dose, were both approximately 180–220 min. Five to fifteen minutes after intramuscular injections of 20 mg prednisolone-hemisuccinate the peak serum concentration was 63·7 ± 7·4 μg/ 100 ml and 30 min later plasma unesterified prednisolone reached its highest level (28·8 ± 2·6 μg/100 ml). The administration of steroids through the rectum induced gradual increases in the levels of serum steroids, reaching a maximum of 25% of the peak serum concentrations observed after oral administration. Plasma betamethasone-17-benzoate levels of 300 ng/ 100 ml were observed after topical application of betamethasone-17-benzoate gel to the skin.

In patients with liver disease, the clearance of betamethasone was very slow compared with that in normal control subjects and significant amounts were retained in the blood 24 h after oral administration, showing that the liver is the most important organ for the metabolism of synthetic glucocorticoid. The concentrations of prednisolone and prednisolone-hemisuccinate in the cerebrospinal fluid were very low after the intramuscular injection of prednisolone-hemisuccinate, confirming the relative impermeability of the blood–brain barrier to polar steroids.
METABOLISM OF TESTOSTERONE AND 5α-REDUCED ANDROGENS BY THE RABBIT PROSTATE AND EPIDIDYMIS: STUDIES IN VITRO AND IN VIVO
Authors: BOOTH W. D. , JONES R.
Published: December 2008

The metabolism of radioactively labelled testosterone, 5α-dihydrotestosterone, 5α-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol by the rabbit epididymis and prostate has been investigated in vitro and in vivo. In vitro, the rate of conversion of testosterone to 5α-reduced androgens was low in both glands. Varying the nature of the tissue preparation, age of animal or incubation medium did not improve the situation substantially. However, the rabbit prostate and epididymis metabolized 5α-reduced androgens readily. The prostate was particularly efficient at interconverting 5α-androstane-3α,17β-diol and 5α-dihydrotestosterone, whereas the capacity of the epididymis to carry out this step was much lower. Small amounts of 5α-androstane-3,17-dione and androsterone were also identified. Both glands interconverted 5α-dihydrotestosterone and 5α-androstane-3β,17β-diol to a comparable degree.

Following the intravenous injection of 3H-labelled testosterone, significant levels of 3H-labelled 5α-dihydrotestosterone were found in the prostate and epididymis within 30 min. Furthermore, 5α-androstane-3α,17β-diol was detected in both glands. In blood plasma, the ratio of radioactively labelled testosterone: 5α-dihydrotestosterone was 2: 1, i.e. similar to that for endogenous steroids. The intravenous injection of 3H-labelled 5α-androstane-3α-17β-diol gave rise to much higher amounts of 5α-dihydrotestosterone in the prostate than in the epididymis, whereas the reverse was found for the levels of unmetabolized diol.

The results indicate that the prostate and epididymis of the adult rabbit differ in their capacity to metabolize 5α-reduced androgens and that both glands depend to a large extent on the relatively high levels of 5α-dihydrotestosterone and 5α-androstanediols present in the peripheral circulation, rather than the metabolism of testosterone in situ.
A SENSITIVE AND SPECIFIC ASSAY FOR 5-METHOXYTRYPTOPHOL IN PLASMA
Authors: LEONE R. M. , SILMAN R. E. , HOOPER R. J. L. , FINNIE M. D. A. , CARTER S. J. , EDWARDS R. , SMITH I. , TOWELL P. , MULLEN P. E.
Published: December 2008

5-Methoxytryptophol (ML) is found in the pineal gland and is known to have biological activity especially as an antigonadotrophic agent, but methods have been lacking for its measurement in the circulation. A gas chromatography–mass spectrometry assay using a trimethylsilyl derivative has been developed for the routine measurement of ML in plasma. The assay is of great specificity and has a sensitivity of 20 pmol/l. Studies on the levels of pineal indoles in the circulation, however, have been hampered by the possibility that extraneous compounds are being cross-measured. Thus the specificity of the routine assay has been further validated by comparing it with an alternative assay system where all the major parameters were changed, i.e. derivatizing reagent, internal standard and mass number. Results that were obtained using both assay systems were closely comparable.
CHANGES IN THE CONCENTRATION OF 5-METHOXYTRYPTOPHOL IN THE CIRCULATION AT DIFFERENT PHASES OF THE HUMAN MENSTRUAL CYCLE
Authors: HOOPER R. J. L. , SILMAN R. E. , LEONE R. M. , FINNIE M. D. A. , CARTER S. J. , GRUDZINSKAS J. G. , GORDON Y. B. , HOLLAND DIANE T. , CHARD T. , MULLEN P. E. , SMITH I.
Published: December 2008

The pineal indole 5-methoxytryptophol (ML) has been shown to have an antigonadal activity when administered to experimental animals, but data on its normal pattern of secretion have been lacking. Using a new gas chromatography–mass spectrometry assay, the concentration of ML at various phases of the human menstrual cycle has been studied. Daily samples were obtained throughout the month from five women with a normal cycle and two women taking an oral contraceptive. In women with a normal cycle levels of ML were found to be significantly lower in the last third of their cycle; this change was not seen in women taking an oral contraceptive who had low levels throughout the month. The changes in concentration of ML did not correlate with the changes in concentration of gonadotrophins.
EFFECTS OF PROSTAGLANDIN E2 AND DIBUTYRYL CYCLIC AMP ON THE HISTAMINE-INDUCED PRODUCTION OF CORTISOL AND CORTICOSTERONE IN ISOLATED CANINE ADRENAL CELLS
Authors: HIROSE T. , MATSUMOTO I. , AIKAWA T.
Published: December 2008

The steroidogenic effect of histamine in isolated adrenocortical cells of the dog was investigated in the presence of prostaglandin E2 (PGE2) and/or dibutyryl cyclic AMP (dbcAMP) in the medium. The effect of histamine, in combination with PGE2, was less than their total individual effects in the production of cortisol, but not of corticosterone. With dbcAMP the effect was just equal to them. However, the combination of histamine, PGE2 and dbcAMP showed an increase twice that of their total individual effects in the production of both steroids. These results indicate that, in the dog, histamine, PGE2 and dbcAMP may act synergistically in the adrenocortical cells.
EPITESTOSTERONE IN THE PLASMA OF THE GOAT DURING PREGNANCY AND AT PARTURITION
Authors: FLINT A. P. F. , BURROW P. V.
Published: December 2008

Epitestosterone, a product of the metabolism of androstenedione by the caprine placenta in vitro, is present in the plasma of the pregnant goat. The maternal concentrations of both epitestosterone and unconjugated oestrogens (mostly oestradiol-17α) in the blood increased before parturition and dropped post partum. Measurement of arteriovenous differences at term indicated that epitestosterone was secreted by the uterus; its production was not dependent on the presence of corpora lutea. It is suggested that the concentration of epitestosterone (+ androstenedione + oestrogens) in maternal plasma may be used as an indicator of placental C-17,20 lyase activity; the slight rise in the concentration of these compounds prepartum suggests a relatively small increase in flow through this enzyme.
INFLUENCE OF ANDROGENS ON THE WEIGHTS OF THE MALE ACCESSORY REPRODUCTIVE ORGANS AND ON THE ACTIVITIES OF MITOCHONDRIAL ENZYMES IN THE EPIDIDYMIS OF THE RAT
Authors: BROOKS D. E.
Published: December 2008

The influence of androgens on the male accessory glands of the rat was assessed in terms of changes in weight and of the specific activity of the mitochondrial enzymes, succinate dehydrogenase, glycerolphosphate dehydrogenase and pyruvate carboxylase, in the epididymis. In some instances, the activity of the cytoplasmic enzymes, hexokinase and phosphofructokinase, was also measured and the influence of androgens on these enzymes was found to be similar to that on the mitochondrial enzymes. After the administration of androgen to castrated rats the specific activity of enzymes reached a new steady state sooner than did epididymal weight. The time taken for the specific activity of the enzymes to reach a new steady state after the removal of androgen was variable, depending on the enzyme and the region of the epididymis. This time was generally longer, however, than the time taken for induction, and in the case of glycerolphosphate dehydrogenase, the decline of activity was slower in the cauda than in the caput. In castrated animals, about 100 times as much androgen was required to attain maximum tissue weight as was required to attain maximum enzyme activity. The epididymis, prostate and seminal vesicles responded similarly to androgen in terms of the dose–response pattern and the time taken for tissue weight to attain a new steady-state value, although the gain in weight of the epididymis relative to its weight in unstimulated control animals was less than the relative gain of the other accessory glands. Enzymes in the cauda epididymidis required lower amounts of androgen to elicit maximum activity than were required by those in the caput. The rate of change in the accessory glands in attaining new steady-state levels of tissue weight and enzyme activity was independent of the dose of androgen except during the first few days of hormone administration. Androgens were the most effective steroids in stimulating an increase of tissue weight and enzyme activity, although some changes were induced by oestradiol-3-benzoate and progesterone.
FAILURE OF MELATONIN TO INCREASE SERUM PROLACTIN LEVELS IN OVARIECTOMIZED RATS SUBJECTED TO SUPERIOR CERVICAL GANGLIONECTOMY OR PINEALECTOMY
Authors: CARDINALI D. P. , FAIGÓN MARÍA R. , SCACCHI P. , MOGUILEVSKY J.
Published: December 2008

The effects of melatonin on serum prolactin levels were examined in ovariectomized rats primed with oestradiol and progesterone, and subjected to bilateral superior cervical ganglionectomy or pinealectomy.

Ganglionectomy resulted in a significant depression of the serum prolactin concentration, as well as in impairment of the prolactin release evoked by administration of steroid. Treatment with melatonin increased serum prolactin in control but not in ganglionectomized rats. Injection of melatonin potentiated the steroid-induced release of prolactin in control rats; this effect of melatonin was not detected in ganglionectomized rats. Pinealectomy did not affect basal prolactin levels, nor impair the release of prolactin evoked by steroid treatment; however, it was effective in blocking the melatonin-induced release of prolactin in vehicletreated rats, as well as the potentiation of steroid-induced prolactin release by melatonin. Intracranial surgery by itself increased prolactin release. These results suggest that systemically administered melatonin needs an intact pineal gland to augment serum prolactin levels.
EFFECT OF CHRONIC PARATHYROIDECTOMY ON CALCIUM METABOLISM IN THE LACTATING RAT
Authors: FRY J. M. , CURNOW D. H. , GUTTERIDGE D. H. , RETALLACK R. W.
Published: December 2008

This study examined the effect of chronic parathyroidectomy (PTX) in rats on calcium homeostasis in milk and serum and on litter growth rate throughout lactation.

Parathyroidectomy was carried out by excision 8 weeks before mating and any animals with evidence of parathyroid regeneration over this time were discarded. Maternal serum and milk samples were collected at days 6, 12 and 20 of lactation and serum samples from the pups were obtained at day 20. Litter growth was measured by weighing the pups daily.

Significantly lower concentrations of ionized and total calcium and significantly higher concentrations of phosphate in the serum were found in the PTX animals compared with the sham-operated controls (P< 0·001). The ratio of ionized to total calcium in serum was significantly lower in the PTX group. The mean total calcium concentration in milk was significantly higher at day 6 in the PTX group (P< 0·05) but was not different from the sham-operated group at days 12 and 20. The ratio of milk calcium to percentage milk solids was the same in both groups of animals at all three sampling periods. Litter growth rate was not significantly different in the two groups up to day 5 or from days 12 to 20. It was lower in the PTX group (P< 0·001) between days 5 and 12. The total concentration of calcium in serum from the young was not significantly different in the two groups.

It was concluded that parathyroid hormone (PTH) is required for normal maternal calcium homeostasis in serum during lactation and therefore its absence may affect milk homeostasis indirectly for part of lactation. In contrast the concentration of calcium in milk and litter growth rate can be maintained at normal levels in late lactation suggesting that PTH is not an essential hormone in the regulation of calcium levels in milk.
PROGESTIN BINDING IN VITRO BY THE BRAIN CELL NUCLEI OF OVARIECTOMIZED OESTROGEN-PRIMED RATS
Authors: SEIKI K. , HARUKI Y. , IMANISHI Y. , ENOMOTO T.
Published: December 2008

The uptake and binding of 17α,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione, a synthetic progestin, by the hypothalamus and cerebral cortex of ovariectomized oestrogen-primed rats was examined in vitro. Uptake of this steroid by the medial basal hypothalamus was higher than that by the remaining hypothalamus and cerebral cortex. The component in the cytosol from whole hypothalami which bound the radioactive progestin sedimented in the 7S region when centrifuged in a sucrose density gradient. The tritiated progestin was displaced by incubation with non-radioactive progestin or progesterone but not by oestradiol-17β, corticosterone or 5α-dihydrotestosterone (1 μmol/l). No 7S binding component was detected in a similar preparation from the cerebral cortex. The nuclear fraction from whole hypothalami extracted by KCl (0·4 mol/l) contained a progestin-binding complex which sedimented at 9S and which was heat-labile and protein in nature. It was concluded that the hypothalamus of ovariectomized oestrogen-primed rats contains progestin-binding material in the cytoplasm and progestin, bound to such material, is transported from the cytoplasm to the nucleus.
DEVELOPMENT OF A RADIOIMMUNOASSAY FOR ADRENAL SPECIFIC PROTEIN: ITS MEASUREMENT IN BIOLOGICAL FLUIDS AND TISSUES
Authors: AL-AWQATI M. A. , ETHERIDGE R. J. , GRUDZINSKAS J. G. , CHARD T.
Published: December 2008

A radioimmunoassay for a new human adrenal specific protein (ASP) is described. The assay has a lower limit of detection of approximately 50 μg/l. The ASP extracted and purified from adrenal glands was used for standardization, radio-iodination and immunization of rabbits. Adrenal specific protein can be detected in normal human serum and plasma (240 ± 80 and 190 ± 60 μg/ml (means ± s.d.) respectively), tissue levels were found in extracts of adrenal medulla, with appreciable amounts in the adrenal cortex, pituitary gland, seminal vesicle and testis, and low levels in all other tissues examined. The highest concentrations in biological fluids were found in seminal plasma and to a lesser extent in milk and menstrual fluid.