bluuebunny/crossref_metadata_2025 huggingface dataset:
Gonadotrophin-releasing hormone secretion (GnRH) in anoestrous ewes and the induction of GnRH surges by oestrogen
Authors: Clarke I. J.
Published: December 2008

Anoestrous ewes were studied to determine the pattern of secretion of gonadotrophin-releasing hormone (GnRH) in the resting state and following a single i.m. injection of 50 μg oestradiol benzoate. In three out of four untreated ewes, two or three GnRH pulses were observed over a 6-h sampling period. In the fourth sheep the GnRH pulse frequency was higher (six pulses/6 h), but GnRH pulse amplitudes were lower. Following oestrogen treatment, GnRH pulses continued until the occurrence of an LH surge 12 h later. In five out of six sheep sampled during the oestrogen-induced LH surge a marked rise in GnRH secretion was seen. In the sixth ewe a large pulse of GnRH was seen at the start of the LH surge followed by increased GnRH secretion.

It is concluded that GnRH pulse frequency is lower, generally, during anoestrus than during the mating season, and that oestrogen treatment of anoestrous ewes causes a surge in GnRH secretion unlike that seen in similarly treated ovariectomized ewes or the natural cyclic preovulatory changes in GnRH secretion.

J. Endocr. (1988) 117, 355–360
Differential effects of testosterone, 5α-dihydrotestosterone and oestradiol-17β on plasma concentrations of LH in castrated ferrets
Authors: Tang Y. P. , Sisk C. L.
Published: December 2008

The biological activity of testosterone often depends on the conversion of testosterone within the target cell to an androgenic or oestrogenic metabolite. The purpose of this study was to compare the relative ability of testosterone and two of its metabolites, dihydrotestosterone (DHT) and oestradiol, to suppress LH secretion in castrated male ferrets. Castrated ferrets were treated with five different doses of steroid by implanting various numbers of s.c. silicone elastomer capsules packed with either testosterone, DHT or oestradiol. The lowest dose of oestradiol (0·1 mm capsule length/100 g body weight, mean estimated total release rate of 25 ng/day) significantly suppressed plasma concentrations of LH in castrated ferrets. Higher amounts of DHT (2·5 mm capsule length/100 g body weight, mean estimated total release rate of 88 ng/day) were required for a significant reduction in plasma concentrations of LH. Concentrations of LH were also significantly lowered by testosterone when administered at a 2·5 mm capsule length/100 g body weight; however, estimated total release rate was 312 ng/day from these capsules. The fact that oestradiol was more effective than DHT, and that DHT was more effective than testosterone in inhibiting LH secretion in castrated ferrets, suggests that in gonadally intact ferrets, testosterone may be converted to DHT or oestradiol within target cells that mediate steroid negative feedback on LH secretion.

J. Endocr. (1988) 117, 461–466
INTERFERON-α MIMICS EFFECTS OF OVINE TROPHOBLAST PROTEIN 1 ON PROSTAGLANDIN AND PROTEIN SECRETION BY OVINE ENDOMETRIAL CELLS IN VITRO
Authors: Salamonsen L.A. , Stuchbery S.J. , O'Grady C.M. , Godkin J.D. , Findlay J.K.
Published: December 2008

Ovine endometrial cells were isolated from ovariectomized oestrogen and progesterone-treated ewes and maintained in primary culture. In-vitro treatment with human interferon-α2 (Roferon, Hoffman La Roche) (5, 50 IU/ml) or purified ovine trophoblast protein 1 (oTP-1, 30 ng/ml) significantly attenuated PGF2α (25±17, 29±17, 28±9%±SEM of control [no in-vitro treatment = 100%] respectively, N=4 ewes) and PGE (11±4, 16±4, 16±5% of control) release from the cultured cells. Fluorography of two dimensional polyacrylamide gel electrophoretic analyses of proteins secreted by the cells following 35S-methionine incorporation, revealed that synthesis and secretion of the same "pregnancy-related" proteins was stimulated by both interferon-α2 and oTP-1. Thus, interferon-α2 (which has sequence homology with oTP-1) acts on the ovine endometrium, eliciting similar biological responses to those of oTP-1.
Effect of phorbol esters and diacylglycerol on steroid metabolism in isolated rat hepatocytes
Authors: Allan C. J. , Skett P.
Published: December 2008

Hepatocytes, isolated from adult male rats and maintained in serum- and hormone-free medium, were pretreated with phorbol esters known to activate protein kinase C (4β-phorbol-12-myristate-13-acetate) and to be inactive in this respect (4α-phorbol and its 12,13-didecanoate ester). Subsequently the cells were assayed for steroid-metabolizing capacity using androst-4-ene-3,17-dione as substrate. The active phorbol ester was seen to inhibit steroid metabolism markedly after 1 h whereas the inactive derivatives did not show this effect. The endogenous activator of protein kinase C (diacylglycerol) was also seen to inhibit steroid metabolism in a manner similar to the 4β-phorbol ester. Hepatic steroid metabolism is, thus, inhibited by activation of protein kinase C and this may be one of the mechanisms by which the regulatory hormones (e.g. growth hormone) affect steroid metabolism in the liver.

J. Endocr. (1988) 118, 19–23
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

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

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

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

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

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

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

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

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

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

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

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

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

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
Intermittent protein–calorie malnutrition in the young rat causes long-term impairment of the insulin secretory response to glucose in vitro
Authors: Swenne I. , Crace C. J. , Jansson L.
Published: December 2008

The effect of a limited period of protein–calorie malnutrition in young rats on insulin secretion in the adult has been studied. Three-week-old rats were weaned onto diets containing 5% protein (low protein; LP) or 15% protein (control; C) and maintained for 3 weeks on their respective diets. A third experimental group was weaned onto standard rat chow (18% protein; normal diet; N). From 6 weeks of age onwards all rats were fed the standard rat chow. Pancreatic islets were isolated from rats aged 3, 6 and 12 weeks and their insulin secretory response to glucose or arginine was tested. At 12 weeks the effects of the secretagogues were also tested using perfusion of isolated pancreatic glands.

In islets from 6-week-old LP rats the glucose-stimulated insulin release was only 25% of that of C and N rats of the same age. Islets from C and N rats responded to arginine in the presence of a low glucose concentration with a small increase in insulin secretion, whereas no such response could be demonstrated in islets from 6-week-old LP rats. Islets from 6- and 12-week-old N rats responded to glucose and arginine. Islets from 12-week-old C rats had a similar response to glucose but did not respond to arginine in the presence of a low glucose concentration. In islets from 12-week-old LP rats the secretory response to glucose remained only 40% that of C and N rats and there was no response to arginine in the presence of a low glucose concentration. The observations on the secretory response of isolated islets from 12-week-old rats were paralleled by similar findings with the perfused, isolated pancreas.

It is concluded that protein–calorie malnutrition early in life persistently impairs the insulin secretory response of the B cell. The individual may, as a consequence, have a lowered ability to respond to nutritional and diabetogenic challenges and it is thus possible that early protein–calorie malnutrition predisposes for diabetes.

J. Endocr. (1988) 118, 295–302
Major secretory protein of human decidualized endometrium in pregnancy is an insulin-like growth factor-binding protein
Authors: Bell S. C. , Patel S. R. , Jackson J. A. , Waites G. T.
Published: December 2008

Pregnancy-associated endometrial α1-globulin (α1-PEG) is quantitatively the major secretory protein product, synthesized and secreted in vitro, of the human decidualized endometrium during pregnancy. This protein has been purified from cytosolic extracts of this tissue and has now been characterized as a 32 kDa somatomedin/insulin-like growth factor (IGF)-binding protein. Immunoreactive α1-PEG isolated from amniotic fluid exhibited identical physiochemical properties and IGF-I-binding characteristics. In cytosolic extracts of pregnancy endometrium, in incubation medium of this tissue and in amniotic fluid, the 32 kDa protein represented the major α1-PEG immunoreactive protein and major IGF-I-binding component. Purified α1-PEG and incubation medium of pregnancy endometrium competed for IGF-I with placental membrane IGF receptors in vitro. The implications of the endometrial source of IGF-I-binding protein are dicussed with reference to the origin of the amniotic fluid and serum small Mr IGF-binding protein and to the suggested paracrine effect upon trophoblast proliferation.

J. Endocr. (1988) 118, 317–328
Day–night rhythm of 5-methoxytryptamine biosynthesis in the pineal gland of the golden hamster (Mesocricetus auratus)
Authors: Galzin A. M. , Eon M. T. , Esnaud H. , Lee C. R. , Pévet P. , Langer S. Z.
Published: December 2008

5-Methoxytryptamine is a potent agonist of presynaptic 5-hydroxytryptamine autoreceptors modulating serotonin release in the central nervous system. This methoxyindole can be synthesized in the pineal gland, but its presence in vivo is still controversial, probably because of rapid catabolism by monoamine oxidase. An improved high-pressure liquid chromatography method, with coulometric detection, has been developed for the simultaneous measurement of melatonin, 5-methoxytryptamine, 5-methoxytryptophol and 5-methoxyindolacetic acid. We have demonstrated a day–night rhythmicity in the amount of 5-methoxytryptamine in the pineal gland of golden hamsters (Mesocricetus auratus) maintained under a long photoperiod (14 h light: 10 h darkness) and pretreated with the monoamine oxidase inhibitor pargyline. Levels of 5-methoxytryptamine were highest at 16.30 h and lowest at 00.30 h. The rhythm for 5-methoxytryptamine appears to be the same as for serotonin (opposite in phase to that of melatonin). The identification of 5-methoxytryptamine has been confirmed by analysis with gas chromatography–mass spectrometry.

J. Endocr. (1988) 118, 389–397
AUTOCRINE REGULATION OF CASEIN TURNOVER IN GOAT MAMMARY EXPLANTS
Authors: Stewart G. M. , Addey C. V. P. , Knight C. H. , Wilde C. J.
Published: December 2008

Local feedback control of milk protein secretion was investigated in goat mammary explants by measuring degradation of newly synthesized casein in the presence of a goat milk whey fraction. Reduced net synthesis of [3H]casein in the presence of the milk fraction was due, at least in part, to its degradation during secretion, suggesting that this process is under autocrine regulation.
INFLUENCE OF GERM CELLS UPON TRANSFERRIN SECRETION BY RAT SERTOLI CELLS in vitro
Authors: LE MAGUERESSE B. , PINEAU C. , GUILLOU F. , JEGOU B.
Published: December 2008

Indirect approach (hypotonic treatment) and direct approaches (co-cultures and conditioned media) were used in order to investigate the effects of germ cells from adult rats upon transferrin secretion by Sertoli cell cultures prepared from 20-day-old rats. Removal of germ cells contaminating the Sertoli cell cultures resulted in a significant decrease in transferrin secretion whereas the addition of crude germ cell preparations or of enriched preparations of pachytene spermatocytes, early spermatids and of liver epithelial cells (LEC) markedly stimulated this parameter. Furthermore, spent media of pachytene spermatocytes and of early spermatids, but not of LEC, also stimulated transferrin production. It is concluded that germ cells normally located within the adluminal compartment of the seminiferous tubules may be capable of controlling their own supply of iron via their influence upon transferrin secretion by the Sertoli cells.
Neuropharmacological analysis of the control of LH secretion in gonadectomized male and female rats: altered hypothalamic responses to inhibitory neurotransmitters in long-term castrated rats
Authors: Almeida O. F. X. , Nikolarakis K. E. , Herz A.
Published: December 2008

The control of LHRH and LH by neurotransmitters and neuromodulators such as the endogenous opioid peptides is essentially the same in intact adult male and female rats: adrenergic and dopaminergic agonists stimulate LH release and opioid agonists inhibit it. Several weeks after gonadectomy, however, the contribution of the endogenous ligands of adrenergic, dopaminergic and opioidergic receptors to the control of LHRH is altered. A detailed pharmacological analysis in long-term ovariectomized females confirmed previous reports that adrenergic and dopaminergic agonists still enhance secretion of LHRH and LH and opioid receptor agonists still suppress it. A similar investigation in long-term castrated males also confirmed previous reports that opioid agonists fail to block LH secretion. In addition, we have found that while adrenergic and dopaminergic agonists cause increases in serum concentrations of LH, adrenoreceptor and dopamine receptor antagonists do not inhibit LH release in long-term castrates. Furthermore, the opioid antagonist naloxone does not raise serum LH levels in either sex after long-term gonadectomy. These observations therefore imply reduced opioidergic, dopaminergic and adrenergic transmission, in relation to LHRH release, after longterm castration. In addition, opioid receptor activity (assessed by responsiveness to an opioid receptor agonist) of female rats is maintained, whereas that of male rats is lost, after long-term gonadectomy.

J. Endocr. (1988) 119, 15–21
The anabolic actions of growth hormone and thyroxine on protein metabolism in Snell dwarf and normal mice
Authors: Bates P. C. , Holder A. T.
Published: December 2008

The individual effects of GH and thyroxine (T4) on protein metabolism were determined in dwarf and normal mice in vivo. The hormone deficiencies of dwarf mice (low serum concentrations of GH and T4) resulted in decreased protein synthesis rates in skeletal muscle and liver, but no difference in synthesis rates in heart. The efficiency of synthesis (g protein/g RNA per day; KRNA) was lower in all three tissues in dwarf compared with normal mice, but effects on RNA concentration were not consistent; there was no change in muscle, a decrease in liver and an increase in heart.

Treatment of dwarf mice for 9 days with either human GH or T4 caused increases in body weight and length. Protein synthesis rates were increased in muscle, liver and heart by either hormone, though much more so with T4 than GH. In muscle and liver both GH and T4 treatment resulted in an increased RNA concentration, but T4 treatment also increased KRNA. In heart, both GH and T4 increased KRNA with no change in RNA concentration. GH caused no significant changes in protein degradation rates so that growth rates were increased. T4 increased degradation rates so that there was no increased net growth in muscle or liver; in heart, T4 did induce increased growth despite the large increase in degradation rate. Tibial length was increased by both hormones; GH treatment of dwarf mice also increased cartilage sulphate incorporation on day 9, but T4 treatment did not, suggesting that bone growth is transient with T4 treatment.

Normal mice showed no changes in growth or tissue protein metabolism in response to GH, but following T4 treatment there was increased protein turnover due to higher tissue RNA concentrations, although only heart growth was increased. Thus normal mice showed almost no net response to GH or T4, but dwarf mice showed a large response to both hormones. The response was different, however, in that GH caused concomitant increases in growth rates whereas T4 altered body tissue proportions.

J. Endocr. (1988) 119, 31–41
Corticotrophin-releasing factor immunoreactivity in the hypothalamus of the rat during the perinatal period
Authors: Chatelain A. , Boudouresque F. , Chautard T. , Dupouyt J. P. , Oliver C.
Published: December 2008

Corticotrophin-releasing factor-41 (CRF-41) immunoreactivity has been measured in hypothalamic extracts of fetal (on days 17, 19 and 21 of gestation), neonatal (1, 2, 3 and 4 weeks of age) and adult rats with a specific radioimmunoassay developed for synthetic rat CRF-41. The hypothalamic content (fmol) and concentration (fmol/mg protein) of immunoreactive CRF-41 gradually increased with age. Chromatography of hypothalamic extracts on Sephadex G-50 Fine showed one single peak of immunoreactive CRF-41 which co-eluted with synthetic rat CRF-41. The retention time of hypothalamic CRF-41 during high-performance liquid chromatography was identical to that of synthetic rat CRF-41 at all stages investigated. These results are consistent with the development of neurones containing CRF-41-like molecules in both the hypothalamus and the median eminence of the fetus, as well as with the hypothalamic control of the cortico-stimulating function of the pituitary gland as early as day 19 of gestation.

J. Endocr. (1988) 119, 59–64
Effects of dietary sodium restriction on peptide stimulation of aldosterone secretion by the isolated perfused rat adrenal gland in situ: a report of exceptional sensitivity to angiotensin II amide
Authors: Hinson J. P. , Vinson G. P. , Whitehouse B. J.
Published: December 2008

The effects of prior sodium depletion on the steroidogenic responses of the rat adrenal gland have been investigated using a method of perfusing the isolated adrenal gland of the rat in situ. Secretion rates of aldosterone in response to the known adrenocortical stimulants ACTH, angiotensin II amide and α-MSH were measured. In each case, the adrenals from sodium-deplete animals responded to a lower dose of the stimulant than the normal animals. This resulted in a 10-fold increase in sensitivity to ACTH, a 100-fold increase in sensitivity to angiotensin II amide, and a 1000-fold increased sensitivity to α-MSH, bringing the threshold concentration required for aldosterone secretion into the physiological range of α-MSH concentrations.

The perfused adrenal gland is particularly sensitive to angiotensin II amide; a bolus administration of 1 amol gave a significant increase in aldosterone secretion in the sodium-deplete group.

These data confirm previous reports of increased adrenal sensitivity to α-MSH and angiotensin II in sodium depletion, and also suggest the existence of intraglandular mechanisms for signal amplification which may be involved in mediating the adrenal response to very small concentrations of stimulant.

J. Endocr. (1988) 119, 83–88
Lack of an effect of morphine or naloxone on the oestrogen-induced LH surge in anoestrous ewes
Authors: Horton R. J. E. , Clarke I. J.
Published: December 2008

To determine whether opioid mechanisms modulate the positive feedback effect of oestrogen on LH secretion, anoestrous ewes were given a single injection of 50 μg oestradiol benzoate (OB), followed by infusions of morphine or naloxone. All sheep were injected i.m. with 50 μg OB at 00.00 h. In experiment 1, sheep were given i.v. infusions of the following: group 1, 12 ml saline/h from 09.00 to 15.00 h (n=12); group 2, 40 mg naloxone/h from 09.00 to 12.00 h (n = 5); group 3, 40 mg naloxone/h from 10.00 to 14.00 h (n = 5); group 4, 10 mg morphine/h from 09.00 to 15.00 h (n = 5); and group 5, 20 mg morphine/h from 09.00 to 15.00 h (n = 5). Jugular blood samples were taken at 30-min intervals to monitor LH surges, which commenced 13.0 ± 0·6 h after injection of OB in control (OB plus saline) ewes. The infusions of naloxone or morphine did not affect the timing or magnitude of the oestrogen-induced LH surge.

To examine the possibility that opioidergic regulation of the LH surge occurred earlier than the infusion regimens in experiment 1, sheep were infused from the time of the OB injection (00.00 h) until 15.00 h. In this experiment (experiment 2), sheep were given i.v. infusions of the following: group 1, 4·2 ml saline/h (n=5); group 2, 20 mg naloxone/h (n=5); and group 3, 20 mg morphine/h (n=5). As in experiment 1, treatment with neither the opioid agonist or antagonist was able to alter the positive feedback response of OB.

These results suggest that neither the timing of the LH surge or the peak concentrations of LH achieved in plasma are influenced by opiates in this model. This suggests that in contrast to the rat, the mechanisms responsible for generating the oestrogen-induced preovulatory-like LH surge in the anoestrous ewe do not involve any endogenous opioid peptide mechanisms.

J. Endocr. (1988) 119, 89–93
Effect of growth hormone on growth and myelination in the neonatal hypothyroid rat
Authors: King R. A. , Smith R. M. , Meller D. J. , Dahlenburg G. W. , Lineham J. D.
Published: December 2008

The possible involvement of a deficit of GH and insulin-like growth factor-I (somatomedin C) (IGF-I/SMC) in mediating the effects of propylthiouracil (PTU)-induced hypothyroidism on body and skeletal growth and myelination was studied in the neonatal rat. Myelination (as assessed by 2′,3′-cyclic nucleotide 3′-phosphohydrolase (CNP) activity), skeletal growth (as assessed by tail length) and body weight of pups from PTU-treated mothers were significantly retarded compared with normal animals or euthyroid controls. At 20 days after birth, plasma GH in hypothyroid animals was undetectable (< 10 μg/l), pituitary GH content was 1 ·2% of control, and plasma, liver and kidney IGF-I/SMC concentrations were 63, 68 and 50% of control values respectively. CNP activity in hypothyroid brain was 52% of normal controls but the concentration of IGF-I/SMC was 113–154% of control. Treatment of hypothyroid animals from day 1 with GH (10 mg/kg body weight per day) restored liver and plasma IGF-I/SMC concentrations at 20 days to values above those of normal animals and euthyroid controls. The concentration of IGF-I/SMC was also significantly (P< 0·001) restored in hypothyroid kidney (79% of normal), but the concentration in brain was unaffected. These observations provide evidence that the GH treatment employed in the present experiments was adequate to restore the deficit. GH treatment had no significant effect on tail length or CNP activity, and only a small (4–24%) effect on body weight at 20 days. Only thyroxine was able fully to restore body weight and substantially restore tail length and CNP activity.

The present study provides strong evidence against an important involvement of GH or IGF-I/SMC in mediating the effects of thyroid hormone on myelination and body growth in the infant rat. It does not, however, rule out the possibility that thyroid hormone is required for the expression of the growth-promoting effects of IGF-I/SMC by other mechanisms such as the expression of the IGF-I/SMC receptor.

J. Endocr. (1988) 119, 117–125
The presence of atrial natriuretic peptide in canine cerebrospinal fluid and its possible origin in the brain
Authors: Marumo F. , Masuda T. , Masaki Y. , Ando K.
Published: December 2008

The presence of atrial natriuretic peptide (ANP) in canine cerebrospinal fluid (CSF) was clearly demonstrated and an attempt was made to determine its origin as either the brain or the atrium. The concentration of ANP in canine CSF was 0·78 ±0·37 pmol/l (n = 31) and showed no evident correlation with that in plasma (r =0·12). Physiological doses of human α-ANP (α-hANP) were continuously infused intravenously into nine dogs, and ANP concentrations in CSF and plasma were examined six to eight times within a 120-min period following this. The ANP level in CSF was not influenced by the systemic administration of α-hANP up to 180 min. Only one low molecular weight peak corresponding to α-hANP could be obtained from the CSF samples, while both low and high molecular weight peaks were observed for plasma ANP by gel permeation chromatography. In the atrial and hypothalamic tissue extracts the same kinds of peaks were also evident.

These results prove the presence of ANP in canine CSF and that it does not come from blood that has seeped across the blood–CSF barriers, but suggest that it may originate from the brain.

J. Endocr. (1988) 119, 127–131
β-Adrenergic blockade counteracts starvational ketosis, but aggravates post-exercise ketosis in non-athletes
Authors: Vahed Y. A. K. , Koeslag J. H. , de V. Lochner J.
Published: December 2008

Post-exercise ketosis is not abolished by glucose ingestion immediately after exercise but is counteracted by simultaneous β-adrenergic blockade. To investigate the effect of β-adrenergic blockade on post-exercise ketosis without the ingestion of glucose, we administered propranolol (1 mg/kg body mass) to 15 carbohydrate-starved people, of whom five had just walked 9 km in 2 h. There were 43 control subjects (no propranolol). The blood concentration of 3-hydroxybutyrate rose from 0·18 ± 0·02 (s.e.m.) mmol/l at 07.00 h to 0·35 ±0 04 mmol/l at 09.00 h whether the subjects had exercised during those 2 h or not (d.f. = 57). The blood concentration of 3-hydroxybutyrate at 15.00 h in the groups not treated with propranolol was not affected by exercise (0·95 ± 0·90 mmol/l; d.f. = 42). Propranolol significantly raised the concentration of 3-hydroxybutyrate at 15.00 h to 1·68 ±0·26 mmol/l when given after exercise (d.f. = 4), but lowered it to 0·46 ±0·07 mmol/l in the non-exercised group (d.f. = 9). This was not accompanied by significant differences in the blood concentrations of glucose, free fatty acid, insulin or glucagon. The difference in response to propranolol administration is probably determined by the alanine and lactate flux from muscle for hepatic oxaloacetate synthesis.

J. Endocr. (1988) 119, 167–171