bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and organ-specific metabolism of calcitonin gene-related peptide in sheep
Authors: Braslis K. G. , Shulkes A. , Fletcher D. R. , Hardy K. J. 
Published: December 2008

ABSTRACT
Calcitonin gene-related peptide (CGRP) is a product of the calcitonin gene with a widespread distribution in neural tissue of the brain, gut and perivascular nerves. Infusion of CGRP produces multiple biological effects, but the physiological significance of these findings will be influenced by the sites and rates of CGRP metabolism.
The metabolic clearance rate and half-life of disappearance of human CGRP were estimated in conscious sheep after infusing CGRP at 1 or 5 pmol/kg per min to steady-state conditions. The particular organs involved in the clearance of CGRP were assessed by measuring the inflow and outflow concentrations across the liver, gut, kidney, lung and brain.
The metabolic clearance rate at steady state was 22·6 ± 2·1 (s.e.m.) and 15·0±1·7 ml/kg per min for the 1 and 5 pmol/kg per min doses respectively. The half-life of disappearance was bi-exponential: 3·6±0·3 min for the first phase and 13·6±1·0 min for the second phase. High-pressure liquid chromatography of plasma at equilibrium revealed only a single peak coeluting with CGRP(1–37): no immunoreactive metabolites were detected. These pharmacokinetic values are intermediate between that of a neurotransmitter and a hormone and are therefore consistent for a peptide with both circulatory and neurotransmitter modes of action. The kidney, with an arterial–renal vein gradient of 14%, and the liver, with a portal– hepatic vein gradient of 25%, were the major organs involved in the clearance of CGRP. The specific organ clearance, however, accounted for only one-third of the whole body metabolic clearance rate of CGRP, suggesting that other more generalized degradative systems are involved, such as endothelial-bound enzymes of blood vessels. This information on clearance and organ-specific metabolism should form a basis for evaluating the physiological roles and modes of action of CGRP.
J. Endocr. (1988) 118,25–31
Reductions in plasma LH concentration and testicular weight in ring doves following intracranial injection of prolactin or growth hormone
Authors: Buntin J. D. , Lea R. W. , Figge G. R. 
Published: December 2008

ABSTRACT
Testicular weights and concentrations of LH in plasma were measured in individually housed adult male ring doves given five daily intracerebroventricular injections of saline–NaHCO3 vehicle (2 μl), ovine prolactin (0·1, 0·5, 1·0 or 2·0 μg/day), turkey prolactin (1·0 μg/day), turkey GH (1·0 μg/day) or ovine GH (1·0 μg/day). Administration of ovine prolactin resulted in a dose-dependent suppression of plasma LH concentration, with values in the two highest dose groups averaging three- to fivefold less than those of vehicle-injected controls. Reductions of similar magnitude were obtained following intracranial administration of turkey, ovine or human GH. Whilst effective in reducing plasma LH, turkey prolactin was less effective than an equivalent dose of ovine prolactin. Testicular regression was observed in all treatment groups which showed a significant decrease in plasma LH concentrations. Because crop sacs remained undeveloped in all treatment groups, it was concluded that these centrally administered hormones acted primarily at the level of the brain or pituitary to exert their suppressive effects. The possibility that prolactin and GH interact with different binding sites to inhibit LH secretion is discussed, together with evidence for a possible role of prolactin and GH in gonadotrophin regulation under normal physiological conditions.
J. Endocr. (1988) 118, 33–40
The parasympathetic nervous system and glucocorticoid-mediated hyperinsulinaemia in the genetically obese (fa/fa) Zucker rat
Authors: Fletcher J. M. , McKenzie N. 
Published: December 2008

ABSTRACT
Lean (Fa/-) and genetically obese (fa/fa) Zucker rats were adrenalectomized at 18 days of age (3 days before weaning) before the onset of hyperinsulinaemia. At 40–41 days of age, basal and glucose-stimulated insulin concentrations did not differ significantly between lean and obese rats. Plasma insulin and glucose concentrations were higher in both phenotypes 24 h after administration of corticosterone (2·0 mg at 12-h intervals). Corticosterone-treated obese rats had higher basal and glucose-stimulated insulin levels than similarly treated lean animals, although plasma glucose concentrations did not differ between phenotypes. The basal plasma insulin concentration of obese rats treated with corticosterone for 24 h was reduced 15, 30 and 45 min after injection of atropine (0·3 mg) without any significant change in the plasma glucose level. Injection of atropine (0·3 mg) 20 min before a glucose load prevented the greater increment in plasma insulin concentration of corticosterone-treated obese rats compared with similarly treated lean animals. Atropine administration (0·3 mg) to intact obese rats at 40 days of age reduced, but did not abolish, their hyperinsulinaemia compared with intact lean animals. It is concluded that (1) pre-weaning adrenalectomy prevents the development of hyperinsulinaemia in genetically obese rats, (2) corticosterone replacement for only 24 h restores the hyperinsulinaemia of obese rats, (3) the differential effects of corticosterone on insulin secretion by lean and obese rats are mediated by the parasympathetic nervous system and (4) the parasympathetic nervous system contributes to, but is not the only cause of, hyperinsulinaemia in intact obese rats.
J. Endocr. (1988) 118, 87–92
Effects of 4-hydroxyandrostenedione and exogenous testosterone on blood concentrations of oestradiol and oviducal embryo transport in the rat
Authors: Forcelledo M. L. , Croxatto H. B. 
Published: December 2008

ABSTRACT
The effect of decreasing oestrogen secretion on the oviducal migration of embryos was investigated in pregnant rats. The reduction of oestradiol production was achieved by administration of the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione (4-OH-A) at various times after coitus.
When 4-OH-A was administered from days 2 to 5, nearly half the embryos were retained in the oviducts at midday on day 5 of pregnancy, in contrast with control animals in which all embryos were transferred to the uterus. Shorter treatments were less effective. The rate of secretion of oestradiol from the ovary on days 2–5 of pregnancy in control rats was low in the morning and high in the afternoon. Treatment with 4-OH-A from days 2 to 5 reduced the secretory surges of oestradiol in the afternoon by 77% without significantly changing the progesterone output. Systemic testosterone levels were significantly increased by this treatment.
To assess whether changes in the transport of ova were due to an increase in testosterone concentrations the influence of exogenous testosterone on embryo transport and oestradiol production was tested. Testosterone administered by subdermal implants from days 2 or 3 to day 5 disturbed embryo transport in a manner similar to that of 4-OH-A. The longest period of testosterone administration decreased ovarian oestradiol production by 82% without changing the secretion of progesterone.
Since ovarian oestradiol production in pregnant rats was reduced similarly by treatment with 4-OH-A and testosterone implants, and since exogenous oestradiol given s.c. on days 2, 3 and 4 counteracted the blocking effect of 4-OH-A and testosterone on embryo transport, the delay in oviducal transport of the embryos can be accounted for by decreased availability of oestradiol rather than increased testosterone production. This interpretation supports a crucial role for endogenous oestradiol in timing the passage of embryos to the uterus in the pregnant rat.
J. Endocr. (1988) 118,93–100
Role of the adrenal medulla in stress-induced hyperinsulinaemia in normal mice and in mice infected with Bordetella pertussis or treated with pertussis toxin
Authors: Sidey F. M. , Dean H. G. , Furman B. L. 
Published: December 2008

ABSTRACT
Intranasal infection of mice with a sublethal dose of Bordetella pertussis or the intravenous administration of purified pertussis toxin resulted in a marked increase in the serum immunoreactive insulin concentration following ether stress. This stress-induced hyperinsulinaemia was not modified significantly by blockade of α2-adrenoceptors with idazoxan, β-adrenoceptors with propranolol, autonomic ganglia with hexamethonium, opioid receptors with naloxone, muscarinic cholinoceptors with atropine or by adrenal demedullation. The effect of pertussis in promoting stress-induced hyperinsulinaemia was mimicked qualitatively by α2-adrenoceptor blockade, adrenal demedullation or ganglionic blockade. However, the serum immunoreactive insulin response to ether stress was smaller in animals subjected to these procedures compared with the response seen in mice infected with B. pertussis or treated with pertussis toxin. Thus, in the mouse, acute stress produces hyperinsulinaemia under conditions in which the release of adrenal medullary catecholamines is prevented, or the inhibitory action on insulin secretion is blocked by α2-adrenoceptor antagonists or by pertussis toxin.
J. Endocr. (1988) 118, 135–140
Steroidal regulation of oestradiol-17β dehydrogenase activity of the human breast cancer cell line MCF-7
Authors: Adams E. F. , Coldham N. G. , James V. H. T. 
Published: December 2008

ABSTRACT
We have examined the direct effects of progestins, oestrogens, peptide hormones and growth factors on oestradiol-17β dehydrogenase (OE2DH) activity of cultures of the human breast cancer cell line MCF-7. Cells were cultured in the presence of steroid or peptide for 6 days, after which the number of cells was determined and cellular OE2DH activity assessed. Progesterone, 6α-methyl-17α-hydroxyprogesterone acetate, norethisterone and d(−)-norgestrel all profoundly inhibited cell mitosis and stimulated reductive (oestrone→oestradiol-17β) and oxidative (oestradiol-17β→oestrone) OE2DH activity. Both oestrone and oestradiol-17β directly stimulated reductive OE2DH activity, but had no effect on the oxidative direction. Oestradiol-17β stimulated cell growth only in phenolred free culture medium. Ovine prolactin, LH, epidermal growth factor and transforming growth factor did not alter OE2DH activity but small stimulatory effects on the growth of MCF-7 cells were exerted by prolactin and a combination of transforming growth factor with epidermal growth factor. It is concluded that these results may explain, at least in part, the alterations in mitotic activity and tissue oestradiol-17β levels observed in breast tissue during varying physiological and pathological conditions, such as during the menstrual cycle and in breast cancers.
J. Endocr. (1988) 118, 149–154
Isolation and structural characterization of thymosin-β4 from a human medullary thyroid carcinoma
Authors: Conlon J. M. , Grimelius L. , Wallin G. , Thim L. 
Published: December 2008

ABSTRACT
An extract of a tumour metastases from a human medullary thyroid carcinoma contained a high concentration (at least 2·9 nmol/g wet weight) of the immunoregulatory peptide, thymosin-β4. The peptide was isolated as a mixture of two components with free and blocked NH2-terminal amino acid residues, the latter form predominating (approximately 98% of the total). The primary structure of the peptide was established by automated Edman degradation after cleavage with cyanogen bromide. The amino acid sequence of human thymosin-β4 was identical to thymosin-β4 previously isolated from calf thymus. Further studies are warranted to determine whether thymosin-β4 production is a useful marker for thyroid and other tumours.
J. Endocr. (1988) 118, 155–159
Ultra rapid blood sampling for the determination of short-term variations in the circulating concentration of oestradiol in man
Authors: Economides D. L. , Howell R. J. S. , Gilbert I. , Perry L. A. , Chard T. 
Published: December 2008

ABSTRACT
Blood was taken from three healthy female and three healthy male volunteers every 20 s for 15 min. The serum level of oestradiol was measured and the pattern of variation assessed by a cusum plot of the sequential data, by autocorrelation of the detrended serial data, and by looking for pulses. In two cases the variation in oestradiol values was greater than that which could be attributed to variation in the assay. Both these subjects showed a significant overall change in values during the sampling period (an increase and a decrease). There was no trend in the remaining four subjects. In two of the six subjects there was significant autocorrelation of detrended sequential levels. Defining a 'pulse' as three times the assay coefficient of variation no more pulses were identified than was expected from random fluctuations. By frequency analysis the two subjects with significant autocorrelation showed periodic fluctuations of approximately 70/h and 9/h respectively. It is apparent that both the rate of sampling and the method of analysis greatly influence the evaluation of pulsatile release of oestradiol.
J. Endocr. (1988) 118, 161–165
Suppression of LH response to gonadotrophin-releasing hormone or oestradiol by ACTH(1–24) treatment in anoestrous ewes
Authors: Dobson H. , Essawy S. A. , Alam M. G. S. 
Published: December 2008

ABSTRACT
Stress is known to result in lowered female reproductive efficiency. The objective of this study was to examine how increased pituitary-adrenal activity may influence gonadotrophin release in anoestrous ewes.
Various doses (0·06–1·0 mg) of a synthetic adrenocorticotrophic hormone (ACTH(1–24)) preparation were injected into ewes 30 min or 3 h before an i.v. injection of 500 ng gonadotrophin-releasing hormone (GnRH). The LH response to GnRH given 30 min after ACTH(1–24) was similar to that after GnRH alone, whereas the response 3 h after ACTH(1–24) was significantly lower, irrespective of the dose of ACTH(1–24). At 30 min and 3 h after ACTH(1–24) the concentrations of cortisol exceeded 50 nmol/l compared with baseline values of < 10 nmol/l.
The effect of ACTH(1–24) on oestradiol-induced LH release was also examined. Those ewes receiving 0·8 mg ACTH(1–24) depot and 50 μg oestradiol benzoate simultaneously had a preovulatory-type increase in LH 14–20 h later, similar to when oestradiol benzoate was given alone. None of the ewes receiving an additional 0·8 mg ACTH(1–24) depot 10 h after oestradiol benzoate had increases in LH concentration. The cortisol concentrations in all ewes receiving either one or two injections of ACTH(1–24) were > 35 nmol/l at 10 h after the oestradiol injection. However, concentrations of progesterone increased from 0·9 ± 0·3 (s.e.m.) nmol/l at the time of the second ACTH(1–24) injection to 2·1 ±0·3 nmol/l after 2 h.
In summary, it would appear that the suppressive effect of ACTH(1–24) on LH secretion induced by GnRH or oestradiol in the anoestrous ewe is not dependent on increased plasma concentrations of cortisol.
J. Endocr. (1988) 118, 193–197
Changes in serum concentrations of inhibin in cyclic pigs
Authors: Hasegawa Y. , Miyamoto K. , Iwamura S. , Igarashi M. 
Published: December 2008

ABSTRACT
A sensitive and specific radioimmunoassay (RIA) system for porcine ovarian inhibin has been developed. Antisera to porcine inhibin of molecular weight 32 000 (32 kDa inhibin) were raised in male chickens. The recognition site of the antiserum used in the present study was the N-terminal region of the α-subunit of 32 kDa inhibin. The antiserum could recognize higher molecular weight forms of inhibin present in porcine follicular fluid as well as the 32 kDa form. The average effective dose and the least detectable amount of inhibin in this RIA were 643 and 30·7 pg/tube respectively. Non-specific effects of serum on the RIA could be overcome by including 100 μl serum from a castrated pig in the standards and by incubating at 30 °C.
Serum concentrations of inhibin fluctuated between 0·6 and 2·5 μg/l during the oestrous cycles of the pigs. The amount of serum inhibin gradually increased from the late luteal phase to the early follicular phase and reached a maximum of 2·48 μg/l at day −4 (day 0 = day of ovulation). Concentrations then decreased rapidly to reach a minimum of 0·6 μg/l. Two small peaks were also observed during the luteal phase, although the concentration was relatively low during this phase. Changes in serum concentrations of oestradiol-17β did not parallel those of inhibin, especially during the luteal phase when serum concentrations of oestradiol-17β remained quite low. Serum concentrations of FSH were inversely related to those of inhibin rather than to those of oestradiol-17β, suggesting that the secretion of FSH during the oestrous cycles of pigs is mainly controlled by ovarian inhibin.
J. Endocr. (1988) 118, 211–219
Influence of nutritional status and oestradiol-17β on plasma growth hormone, insulin-like growth factors-I and -II and the response to exogenous growth hormone in young steers
Authors: Breier B. H. , Gluckman P. D. , Bass J. J. 
Published: December 2008

ABSTRACT
Plasma GH profiles and circulating concentrations of plasma insulin-like growth factors-I and -II (IGF-I and -II) were examined in 20 steers on either high (3% dry matter of body weight per day) or low (1% dry matter of body weight per day) planes of nutrition with or without an implant of oestradiol-17β. The response of plasma IGF-I and -II to a bolus injection of bovine GH (bGH) was also investigated.
Reduced feeding significantly (P <0·01) increased the mean concentration, peak height and integrated area of plasma GH. Treatment of steers with oestradiol at low nutrition significantly increased baseline GH concentrations. Treatment of steers with oestradiol at high nutrition significantly (P <0·05) increased mean, baseline, peak height, and integrated area of plasma GH. GH pulse frequency was not changed by either nutritional plane or oestradiol treatment.
Basal concentrations of plasma IGF-I were significantly (P <0·01) decreased by reduced feeding in both the oestradiol-treated and the control group. Treatment with oestradiol increased (P <0·01) basal plasma concentrations of IGF-I at both high and low levels of nutrition. After i.v. injection of bGH (0·1 mg/kg body weight), an increase in plasma IGF-I was observed only in steers at high nutrition. Basal concentrations of plasma IGF-II were not altered by nutritional manipulations but were significantly (P <0·001) increased by oestradiol treatment. After bGH infusion only steers at high nutrition showed an increase in plasma IGF-II. Significant correlations were observed between daily body weight gain and plasma concentrations of IGF-I (r= 0·91, P<0·001, n = 20) and also between the capacity of the high-affinity hepatic somatotrophic receptor and plasma IGF-I (r= 0·89, P <0·001, n= 10).
Decreased plasma concentrations of IGF-I at a low level of nutrition may abolish the growth-promoting activity of circulating GH. The increase in both GH secretion and the number of somatotrophic receptors with oestradiol treatment may represent a coordinated response of the somatotrophic axis leading to enhanced IGF-I and -II production and improved growth rate. The inferential relationships between the capacity of the high-affinity somatotrophic receptor, plasma concentrations of IGF-I and growth rates suggest that active modulation of somatotrophic receptors is an important regulatory constituent of the somatotrophic axis.
J. Endocr. (1988) 118, 243–250
Gestational changes in prostaglandin synthase activity of ovine cotyledonary microsomes
Authors: Rice G. E. , Wong M. H. , Thorburn G. D. 
Published: December 2008

ABSTRACT
The capacity of cotyledonary microsomes, prepared from pregnant ewes (20–145 days of gestation), to metabolize exogenous arachidonic acid was quantified using a radiolabel technique. During gestation, the capacity of microsomes to metabolize arachidonic acid increased 25-fold, from 0·36±0·06μmol arachidonic acid/incubation (n = 8) at <100 days of gestation to 9·06±1 ·02μmol arachidonic acid/incubation at 130–145 days of gestation (n = 5; P<0·05). Arachidonic acid was metabolized to prostaglandin E2 and F2α, as determined by thin-layer chromatography and reverse-phase high performance liquid chromatography. The profile of prostaglandins synthesized by cotyledonary microsomes did not change throughout gestation. These data suggest that the increase in cotyledonary prostaglandin synthesis that occurs during late gestation and at term may reflect an increase in the tissue content of prostaglandin H2 synthase.
J. Endocr. (1988) 118, 265–270
Effects of bromocriptine on corticotrophin, melanotrophin and corticosteroid secretion in dogs with pituitary-dependent hyperadrenocorticism
Authors: Rijnberk A. , Mol J. A. , Kwant M. M. , Croughs R. J. M. 
Published: December 2008

ABSTRACT
Dogs with spontaneous pituitary-dependent hyperadrenocorticism were divided into two groups, one with normal plasma concentrations of α-MSH (normal α-MSH dogs, n = 26) and the other with high plasma concentrations of α-MSH (high α-MSH dogs, n= 14), on the presumption that high α-MSH concentrations indicated a parent cell of pars intermedia origin.
The urinary corticoid/creatinine ratios of the high α-MSH dogs were significantly higher than those of the normal α-MSH dogs. The percentage decrease of the corticoid/creatinine ratios following dexamethasone administration was significantly higher in the normal α-MSH dogs than in the high α-MSH dogs. Dexamethasone resistance occurred in both the normal α-MSH dogs (4 out of 26) and the high α-MSH dogs (7 out of 14), indicating a relative rather than an absolute difference.
The short-term effect of orally administered bromocriptine, at a dose (10 μg/kg body weight) known to be effective in lowering prolactin concentrations in dogs, was investigated by measuring concentrations of cortisol, ACTH and α-MSH in plasma at 4, 6 and 8 h after administration. Significant decreases were observed for cortisol in both groups and for α-MSH only in the high α-MSH dogs.
The effect of 5 days of bromocriptine administration (10 μg at 12-h intervals) was assessed by measurements of urinary corticoid/creatinine ratios. Considering both groups as a whole, only the corticoid/creatinine ratios of the high α-MSH dogs decreased significantly on the first day of treatment. In each group there was one dog in which bromocriptine administration lowered the corticoid/creatinine ratios for several days, but the values stayed above the reference range and the animals did not recover.
It is concluded that high α-MSH concentrations are not unambiguously associated with the theoretically expected characteristics of pars intermedia disease. The results indicate that the pituitary lesions causing hyperadrenocorticism may not maintain the regulation characteristics of the lobe of origin.
J. Endocr. (1988) 118, 271–277