bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the ovaries in inducing mammogenesis in pregnant pigs
Authors: Buttle H. L.
Published: December 2008

Ovariectomy, but not removal of the corpora lutea, of gilts at mid-pregnancy delayed the onset of lobuloalveolar development in the mammary glands. Lactogenesis at the time of parturition was delayed by both ovariectomy and removal of the corpora lutea.

J. Endocr. (1988) 118,41–45
Secretion of progesterone and prostaglandins by cells of bovine corpora lutea from three stages of the luteal phase
Authors: Rodgers R. J. , Mitchell M. D. , Simpson E. R.
Published: December 2008

The secretion of prostaglandins (PGs) by bovine corpora lutea was investigated. Corpora lutea from the early, early-mid and late-mid stages of the luteal phase were dissociated by collagenase treatment and cultured in monolayer in Dulbecco's modified Eagle's medium containing 10% (v/v) fetal calf serum. Treatment with either LH (100 ng/ml) or dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) had no effect on progesterone secretion by early luteal phase cells but stimulated progesterone secretion two- to fourfold by cells from the latter stages. The secretion rates, per μg cell protein, of 6-keto-PGF1α, PGE2 and PGF2α were substantially greater in cells from the early luteal phase than in those from the latter stages, however, all changes in PG secretion in response to treatments were qualitatively similar between cells from the three stages of the luteal phase. The secretion rate of 6-keto-PGF1α was greater than that of PGE2 or PGF2α and was inhibited by treatment with indomethacin (28 μmol/l) but unaltered by treatment with LH, dbcAMP or butyrate (1 mmol/l). Secretion of PGE2 was inhibited by indomethacin but stimulated two-to threefold by treatment with either dbcAMP or butyrate. Secretion of PGF2α was minimal and not inhibited further by treatment with indomethacin, but was stimulated 10- to 40-fold with dbcAMP. Indomethacin treatment inhibited the stimulatory effect of dbcAMP; butyrate had no effect on PGF2α secretion. Treatment with LH had no effect on any of the PGs measured. In these experiments the secretion of progesterone appeared unrelated to any changes in the secretion of PGs. Thus it would appear that the production of progesterone by bovine luteal cells in culture is not related nor dependent upon the secretion of 6-keto-PGF1α, PGE2 or PGF2α, and that LH/cAMP does not regulate the secretion of PGs since LH had no effect on PG secretion and since the effects of dbcAMP appeared not to be through a cAMP-dependent pathway.

J. Endocr. (1988) 118, 121–126
Thyrotrophin-blocking antibodies in goitrous primary hypothyroidism: detection by a highly sensitive bioassay and determination of site of action
Authors: Atkinson S. , Hardwick M. , Kendall-Taylor P.
Published: December 2008

Using a highly sensitive bioassay technique, the presence of antibodies capable of blocking the stimulation of thyrocyte function by TSH has been investigated in the sera of a group of 50 patients with primary hypothyroidism. TSH-blocking activity was detected in immunoglobulin (IgG) preparations from the sera of 13 patients (26%). All 13 IgG preparations blocked both TSH-stimulated iodide uptake and cyclic AMP generation (Spearman's rank correlation = 0·6, p = 0·02). However, only one IgG preparation blocked dibutyryl cyclic AMP-stimulated iodide uptake.

The presence of TSH-blocking antibody activity was associated with goitrous (ten out of thirteen patients) as well as atrophic (two out of thirteen patients) primary hypothyroidism. Furthermore, TSH-blocking activity was not associated with other thyroid autoantibodies, as thyrotrophin-binding-inhibiting immunoglobulins and anti-TSH antibodies were undetectable in all cases and there was no correlation between TSH-blocking activity and the presence or titre of anti-thyroglobulin or anti-microsomal antibodies.

This study indicates that TSH-blocking antibodies are present in the serum of some patients with primary hypothyroidism and are directed towards a site, presumably adjacent to or contiguous with the TSH receptor, that is not the binding site for TSH. The coexistence of TSH-blocking activity and goitre in the majority of these patients implies that these antibodies, although capable of blocking TSH-stimulated thyroid hormone biosynthesis, do not necessarily inhibit the mitogenic action of TSH in vivo.

J. Endocr. (1988) 118, 141–147
Monolayer cultures of pancreatic islet cells from adult rats: effect of 2-deoxyglucose
Authors: Aoki M. , Kagawa S. , Yamamura T. , Matsuoka A. , Utsunomiya J.
Published: December 2008

Techniques for the monolayer culture of pancreatic islet cells from adult rats and the responsiveness of B cells are described. Whole pancreatic tissue was enzymatically dispersed and then cultured for 30 days in tissue culture medium 199 containing 5·5 mmol glucose/l, with or without 1 mmol 2-deoxyglucose/l. In the absence of 2-deoxyglucose, the responsiveness of B cells diminished to almost zero by day 15 and islets degenerated. In contrast, addition of 2-deoxyglucose to the medium resulted in a selective degeneration of fibroblasts, yielding monolayers that consisted mostly of islet cells. In this stationary system in which monolayers of islet cells were maintained in medium with 2-deoxyglucose, insulin secretion from B cells on days 15 and 30 increased in a dose-dependent fashion in response to increasing concentrations of glucose, leucine and 2-ketoisocaproate. Similarly, when exposed to 16·7 mmol glucose/l, perifused B cells showed a biphasic pattern of insulin secretion on day 15. Addition of 10 μmol forskolin/l and 200 nmol 12-O-tetradecanoyl phorbol13-acetate/l remarkably enhanced this response. Likewise, the response to 10 mmol leucine/l or 10 mmol 2-ketoisocaproate/l was biphasic. These results suggest that these monolayer cultures retain the functional properties of the adult rat pancreas, and may be useful not only as a model for the in-vitro study of B cell function, but also for implantation.

J. Endocr. (1988) 118, 173–178
Somatostatin levels and binding in duodenal mucosa of rabbits with ligation of the pancreatic duct
Authors: Guijarro L. G. , Arilla E.
Published: December 2008

Atrophy of the exocrine pancreas was induced in rabbits by pancreatic duct ligation. Somatostatin concentration and binding in cytosol from rabbit duodenal mucosa were studied after 6 and 14 weeks of pancreatic duct ligation. Somatostatin-like immunoreactivity was significantly increased in the duodenal mucosa in both periods. Scatchard analysis showed a parallel increase in the number of binding sites rather than a change in their affinity. The physiological significance of these findings remains to be clarified.

J. Endocr. (1988) 118, 227–232
Effect of glucose concentrations on functional maturation of monolayer-cultured B cells from the rat pancreas
Authors: Wakabayashi S. , Kagawa S. , Yamashita K. , Matsuoka A.
Published: December 2008

The effect of two concentrations of glucose on the maturation of the response of B cells was studied in pancreatic monolayer cultures of the neonatal rat using a perifusion system. After exposure for the initial 3 days to a medium with 5·5 mmol glucose/l and 10 μmol iodoacetic acid/l (day 3), in order to delete fibroblasts selectively, monolayer cultures were kept for a total of 12 days in medium with either 5·5 or 16·7 mmol glucose/l alone. On day 3, B cells responded in a monophasic fashion, with no significant second phase, to acute challenge with 16·7 mmol glucose/1. At a concentration of 10 mmol/l, leucine and 2-ketoisocaproate both produced only minimal increases in the second phase of secretion above the basal level. In contrast, B cells on day 7 cultured in 5·5 mmol glucose/l showed a biphasic response to glucose, leucine and 2-ketoisocaproate. The magnitude in response to glucose was well preserved at day 15 of culture, whereas the stimulatory effects of leucine and 2-ketoisocaproate decreased to 24–57% of that of B cells on day 7. Moreover, B cells on day 7 cultured in 16·7 mmol glucose/l responded in a biphasic manner to glucose, the response being 65% of that of B cells in 5·5 mmol glucose/l. Additionally, the response to leucine and 2-ketoisocaproate still appeared to be monophasic. At day 15 of culture, however, the response of B cells in 16·7 mmol glucose/l to glucose was 105%, to leucine 245% and to 2-ketoisocaproate 127% of that of B cells in 5·5 mmol glucose/l. In conclusion, these results suggest that cultivation in medium with 5·5 mmol glucose/l could induce precocious development of an adult pattern of insulin secretion compared with that in 16·7 mmol glucose/l and, in addition, that the medium with 16·7 mmol glucose/l is superior for long-term culture to the medium with 5·5 mmol glucose/l.

J. Endocr. (1988) 118, 303–310
A comparison of the dynamics of secretion of human growth hormone and LH pulses
Authors: McIntosh R. P. , McIntosh J. E. A. , Lazarus L.
Published: December 2008

Patterns of hypothalamic stimulation causing pituitary hormone release cannot be studied directly in humans; one possible approach is to make inferences from the nature of the response of the target organ as revealed by patterns of pituitary hormones in blood. Replicated, precise assay of LH in frequently sampled blood of women at differing stages of the menstrual cycle has demonstrated previously that secretion of this hormone is compatible with a model of discrete, instantaneous episodes of LH output, which are assumed to be stimulated by isolated bursts of increased stimulatory hypothalamic gonadotrophin-releasing hormone. However, similarly detailed measurements of the dynamic secretion patterns of GH in women reported here, revealed much slower rates of increase of GH concentrations (median time to maximum concentration 38 min) in comparison with LH (13 min) assayed in the same blood samples. These rise rates of GH were uncorrelated with the final amplitude of the peak and were observably discontinuous in half the peaks. Simultaneous i.v. injection of a bolus of mixed GRF and GnRH produced similar dynamics of pituitary release of GH and LH. Thus differences in patterns of natural release of the two hormones appear to be contributed to by differences in the modes of hypothalamic stimulation. Current understanding of control of GH release in animal models suggests that the slow-rising, frequently discontinuous natural peaks of GH in human blood are likely to be caused by interaction between the withdrawal of inhibitory hypothalamic somatostatin and the increased secretion of stimulatory GRF.

J. Endocr. (1988) 118, 339-345
The role of growth hormone in diabetes mellitus
Authors: Holly J. M. P. , Amiel S. A. , Sandhu R. R. , Rees L. H. , Wass J. A. H.
Published: December 2008

The insulin and growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis are two endocrine systems that are interlinked at many levels. GH is one of the glucose counter-regulatory hormones, rising in response to hypoglycaemia, it has both intrinsic hyperglycaemic actions and causes insulin resistance. Both IGF-I and its receptor have high structural and functional homology to insulin and its receptor. Insulin can regulate IGF-I production, acting on the GH receptor or at a post-receptor site. Conversely IGF-I is thought to have a permissive effect on the pancreatic insulin response to glucose.

Growth is compromised in poorly controlled diabetic children; however, a causal link with altered GH/IGF-I levels has not been proven. Insulin-dependent diabetes clearly causes derangements in the GH/IGF-I axis. In poorly controlled diabetics GH levels are invariably raised whilst normal or low levels of IGF-I are found, indicating a dissociation between the two factors. Altered IGF-binding protein levels are also found, with high levels of small binding protein and low levels of large binding protein. These derangements are probably the result of interactions at many levels although the exact mechanisms are not fully understood.

Raised GH levels could result from altered hypothalamic/pituitary control or reduced feedback inhibition. The latter could, in turn, result from low IGF-I levels, reduced availability of IGF-I to relevant receptors or increased levels of inhibitors (possibly the small binding protein). Low IGF-I levels could be directly due to deficient insulin levels or simply to lack of available circulating binding protein.

Alternative or altered molecular forms of circulating GH in diabetes seem unlikely on present evidence.

That GH has an effect on glycaemic control is most evident from the abnormal glucose tolerance seen in acromegalics, but is also seen with physiological GH variations such as during the pubertal growth spurt. In diabetics the derangements to the GH/IGF-I axis, caused by poor metabolic control, leads to aggravation of the metabolic problems.

Altered GH/IGF-I levels have been implicated in the long-term complications associated with diabetes, and whilst GH/IGF-I are not essential for the early changes involved in these complications they may still play an important role in their development, especially proliferative retinopathy.
Activation of the adrenal cortex or the peripheral sympatho-adrenomedullary system does not necessarily influence milk ejection in the rat
Authors: Lau C.
Published: December 2008

Following a 5-h isolation period, primiparous rats have the same milk supply on days 8/9 and 13/14 post partum, yet in response to suckling they release a greater amount of milk at the latter time. Inasmuch as stress is known to inhibit lactation and handling of the pups is stressful to the dams, the question arose as to whether separation from pups before nursing constitutes a greater stress for the dam at the earlier stage of lactation. This possibility was explored in the present study. As an index of stress, changes in plasma corticosterone were measured from chronically cannulated dams. In addition, the role of adrenal hormones and the peripheral sympathetic nervous system in the regulation of milk ejection under these experimental conditions was assessed following bilateral adrenalectomy and treatment with pentolinium, a ganglionic blocker which does not cross the blood–brain barrier. Corticosterone pellets were implanted subcutaneously following adrenalectomy in order to maintain proper lactation. From the results obtained, lactators demonstrated a greater increase in plasma adrenocorticosteroid levels in response to nursing on day 8/9 than on day 13/14 post partum, but milk yield was significantly less at the earlier than at the later stage of lactation. Adrenalectomy in conjunction with corticosterone replacement pellets did not alter milk supply or milk release. The subsequent treatment with pentolinium did not affect milk ejection. Pups still ingested less milk on day 9 than on day 13/14. It is suggested here that the isolation/suckling condition imposed on lactators may be more stressful earlier in lactation. Inasmuch as removal of the adrenal hormones along with ganglionic blockade did not modify the amount of milk ingested by the pups, it is concluded that the smaller milk release observed on day 9 post partum does not result from a direct suppression by the adrenal hormones or by the peripheral sympathetic nervous system on milk ejection.

J. Endocr. (1988) 118, 399–405
Stimulation of release of growth hormone from the anterior pituitary by α-melanocyte-stimulating hormone: a possible mechanism for induction of pseudopregnancy in the rat
Authors: Volosin M. , Celis M. E.
Published: December 2008

In hypophysectomized rats on day 1 of dioestrus, as well as on day 4 of pseudopregnancy, α-MSH (continuous infusion of 1 μg/h) failed to maintain serum concentrations of progesterone. On the other hand, α-MSH did not modify the increase induced by ACTH (1 μg/μl as an infusion plus two additional daily injections of 30 μg/μl), prolactin (200 μg/0·2 ml at 12-h intervals) or GH (300 μg/0·2 ml twice daily) on serum concentrations of progesterone in such rats. However, in intact rats α-MSH caused a significant rise in serum concentrations of GH on day 1 and day 2 of dioestrus. Continuous infusion of α-MSH produced an increase in serum concentrations of GH at 12.00 and 14.00 h on day 1 of dioestrus and at 07.00 h on day 2.

It is therefore suggested that α-MSH may exert its effect by facilitating the secretion of GH, which in turn may induce the release of progesterone.

J. Endocr. (1988) 118, 465–470
Plasma concentrations of insulin-like growth factor-I and insulin in the infant calf: ontogeny and influence of altered nutrition
Authors: Breier B. H. , Gluckman P. D. , Bass J. J.
Published: December 2008

The developmental pattern of plasma insulin-like growth factor-I (IGF-I) and insulin in calves subject to different patterns of weaning was investigated from birth until the age of 6 months. Fifteen male Friesian calves were fed on whole milk (10% of body weight per day) for the first 8 weeks after birth, then allocated into three balanced groups. Group 1 was weaned at 8 weeks; group 2 was weaned at 8 weeks, returned to milk-feeding at 13 weeks to be weaned again at the age of 16 weeks; group 3 was weaned at 12 weeks. After weaning the calves were fed on concentrates and lucerne hay.

At birth, circulating concentrations of IGF-I correlated with birth weight (r = 0·78, P< 0·001). There was a significant (P<0·001) fall in plasma IGF-I from birth (40·3 ± 2·5 μg/l) until 5 weeks (23·8± 1·3 μg/l), and then a gradual (P<0·01) rise until week 8 (35·0 ± 2·2 μg/l). Weaning (groups 1 and 2 after week 8) caused a significant (P<0·01) decrease in plasma IGF-I (20·5 ± 1·9 μg/l); thereafter plasma levels of IGF-I rose gradually (P<0·01) in animals fed on concentrates. The milk-fed calves (group 3) showed a progressive increase in plasma IGF-I with age until they were weaned at 12 weeks (51·0 ± 3·4 μg/l); IGF-I levels then decreased to be similar to group 1 (32·5 ± 2·1 μg/l). When group 2 was returned to milk-feeding, plasma IGF-I concentrations increased to 58·2 ±3·8 μg/l within 4 days and then continued to rise gradually until decreasing upon weaning. The age-related increase in the plasma concentration of IGF-I after 6 weeks was parallel in milk- and concentrate-fed calves.

Binding of 125I-labelled bovine GH to hepatic membranes of neonatal calves was low at birth (specific binding; 1·56 ±0·29% n=3). Somatotrophic binding was apparent at 6 weeks (6·43 ±0·42%, n = 3) and increased (9·2± 1·1%, n=3) at the age of 12 weeks. Thus the early postnatal changes in plasma IGF-I may reflect the transition from GH-independent to GH-dependent IGF-I secretion.

Plasma concentrations of insulin at birth correlated with IGF-I (r = 0·54, P<0·05). However, regression analysis suggested no effect of insulin on birth weight independent of IGF-I. Plasma insulin levels rose gradually until weaning and thereafter were significantly (P<0·01) higher in the milk- than concentratefed calves.

Major changes in plasma concentrations of IGF-I related to monogastric (milk feeding) or ruminant (concentrate feeding) nutrition of the young calf are demonstrated. They may be mediated through changing plasma insulin concentrations. An age-dependent prepubertal rise in plasma IGF-I apparently independent of nutritional factors commenced with the appearance of functional somatotrophic receptors in the liver.

J. Endocr. (1988) 119, 43–50
Growth hormone-deficient dwarfism in the rat: a new mutation
Authors: Charlton H. M. , Clark R. G. , Robinson I. C. A. F. , Goff A. E. Porter , Cox B. S. , Bugnon C. , Bloch B. A.
Published: December 2008

Mutations in animals have provided insight into many aspects of normal and pathological human physiology. This paper reports the discovery and initial characterization of a new mutant dwarf rat. The mutation, inherited as an autosomal recessive, arose spontaneously in a breeding colony of Lewis rats at the Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, Oxford, U.K., in 1985 and the strain has now been established both in Oxford and at Mill Hill. Body growth in the mutant is retarded such that at 3 months of age both males and females weigh approximately 40% less than their normal litter-mates, and continue to grow at a slower rate.

The mutants show a selective reduction in pituitary GH synthesis and storage (pituitary GH concentrations were approximately 10% of normal in males and 6% in females). The concentration of their anterior pituitary trophic hormones (LH, TSH, prolactin and ACTH) were within the normal range in dwarf animals. Exogenous GH treatment for 5 days resulted in an increase in growth rate from 1·5 ± 0·3 to 3·9 ± 0·4 g/day in male mutants, and 0·8 ± 0·2 to 3·1 ±0·1 g/day in females. Longitudinal bone growth rates were more than doubled by this treatment from 49 ± 5 to 100 ±10 μm/day in females and from 52 ± 11 to 131 ± 16 μm/day in males.

Dot blot and Northern blot analysis of pituitary mRNA extracts revealed that the GH message in mutants was between 20 and 25% of normal, and that the GH transcript was of normal size.

Immunoreactive GH-releasing factor (GRF) and somatostatin were present in the dwarf hypothalamus, and exogenous GRF released small amounts of GH in vivo but in proportion to the pituitary GH content. This mutant rat, which shows a selective pituitary GH deficit, may provide a useful new model for studying the endocrinology of growth.

J. Endocr. (1988) 119, 51–58
Treatment with bovine follicular fluid suppresses follicular development in gonadotrophin-releasing hormone-treated anoestrous ewes
Authors: Hunter M. G. , Hindle J. E. , McLeod B. J. , McNeilly A. S.
Published: December 2008

The role of FSH in gonadotrophin-releasing hormone (GnRH)-induced follicular development in anoestrous ewes was investigated using injections of bovine follicular fluid (bFF) to reduce plasma FSH levels. Groups of five animals were treated for 12 h with GnRH (250 ng at 2-h intervals) alone, GnRH plus bFF or saline alone, or for 36 h with GnRH alone, GnRH plus bFF or bFF alone. The administration of bFF (1·5 ml s.c. at 8-h intervals) significantly (P<0·05) reduced mean plasma FSH levels, but with the exception of animals treated with bFF alone, had no effect on LH levels. Treatment with bFF alone for 36 h resulted in a significant (P<0·05) increase in LH concentrations. There was considerable variation in the number of follicles ≥2 mm in diameter in the treatment groups. The mean diameter, oestradiol secretion and number of 'oestrogenic' follicles were significantly (P<0·01) reduced in ewes treated with GnRH plus bFF or bFF alone for 36 h compared with those treated with GnRH alone. Testosterone secretion by the follicles was not affected by treatment.

These results confirm previous findings that treatment with bFF decreases circulating FSH levels in anoestrous ewes and, moreover, that concurrent administration of bFF and GnRH inhibits the follicular maturation that is induced by treatment with GnRH alone, suggesting that FSH as well as LH is required for follicular maturation in the ewe.

J. Endocr. (1988) 119, 95–100
Characteristics of milk ejection, associated intramammary pressure changes and oxytocin release in the mare
Authors: Ellendorff F. , Schams D.
Published: December 2008

The neuroendocrine reflex theory of milk ejection was investigated in the horse under natural suckling conditions. To this end 12 lactating mares were provided with acute jugular catheters and with intramammary pressure (IMP) recording catheters. The foal had free access to the contralateral mammary complex. Intramammary pressure could thus be recorded while blood was drawn simultaneously for oxytocin analysis from the undisturbed animal. Suckling periods associated with a characteristic increase in IMP lasted significantly longer than unsuccessful nursing attempts. Elements of successful sucklings involved physical stimulation of the mammary gland, a quiet phase and a sudden increase in IMP. Successful suckling took place at about 20-min intervals with a wide range from < 5 min to > 100 min. Between 5 and 10 mU oxytocin i.v. were sufficient to evoke an increase in IMP identical in shape and duration to a naturally induced increase in IMP. Mean peak oxytocin levels reached 15·8 pmol/l plasma, with a maximal release of 39 pmol/l. In the majority of cases (> 80%) peak oxytocin release did not occur until after the increase in IMP; in some cases an oxytocin surge was not detectable at all, despite a milk ejection-associated increase in IMP. In three cases increase in IMP could be observed while the foals were away from the mother with no signs of any intention to suckle. The data indicate that in the horse some elements of the neuroendocrine reflex, such as tactile stimulation of the teat and a surge of oxytocin before an increase in IMP, are facultative and not essential for normal milk ejection.

J. Endocr. (1988) 119, 219–227
Facilitated calcium mobilization and inositol phosphate production in the priming effect of LH-releasing hormone in the rat
Authors: Mitchell R. , Johnson M. , Ogier S.-A. , Fink G.
Published: December 2008

The ability of LHRH to induce Ca2+ mobilization and production of inositol phosphates in rat anterior pituitary tissue in vitro was investigated in relation to the self-priming effect of LHRH. Prior exposure to LHRH (which caused a characteristic potentiation of subsequent secretory responses) specifically enhanced LHRH-induced inositol phosphate production and mobilization of intracellular Ca2+ stores. LHRH-induced influx of Ca2+ through dihydropyridinesensitive Ca2+ channels was unaltered, as was ligand binding to LHRH receptors. These data suggest that a novel facilitation of signalling may occur in the phospho-inositide-Ca2+ mobilization response mechanism during LHRH priming, and that this may represent an important means of regulating cellular responsiveness in gonadotrophs.

J. Endocr. (1988) 119, 293–301
Effect of tamoxifen on oestrogen binding, lipid and lipoprotein concentrations and blood clotting parameters in premenopausal women with breast pain
Authors: Caleffi M. , Fentiman I. S. , Clark G. M. , Wang D. Y. , Needham J. , Clark K. , La Ville A. , Lewis B.
Published: December 2008

As part of a controlled trial of the use of tamoxifen for the treatment of mastalgia, some of the metabolic and haematological effects of this agent were measured. A panel of haemostatic variables including prothrombin time, kaolin cephalin clotting time, fibrinogen, euglobulin lysis time, factor VII, factor VIII, protein C and anti-thrombin III were determined. In addition, levels of sex hormone-binding globulin and both total and free oestradiol were estimated. No alteration in clotting function was found during the administration of tamoxifen, although hepatic function did alter during this period with an increase in concentration of sex hormone-binding globulin. There was a significant increase in total oestradiol and free oestradiol although the percentage of biologically available free oestradiol fell slightly during the course of tamoxifen treatment. There was a slight reduction in low-density lipoprotein cholesterol with an increase in HDL2, a subclass of high-density lipoprotein (HDL) cholesterol, consistent with an oestrogen-agonist effect. These data suggest that tamoxifen administration does not adversely influence haemostatic mechanisms or lipoprotein metabolism in the short term.

J. Endocr. (1988) 119, 335–339
Sensitization and desensitization of human thyroid cells in culture: effects of thyrotrophin and thyroid-stimulating immunoglobulin
Authors: Kraiem Z. , Alkobi R. , Sadeh O.
Published: December 2008

Using an in-vitro system of cultured human thyroid cells and cyclic AMP (cAMP) accumulation as an index of cell stimulation, we compared TSH and thyroid-stimulating immunoglobulin (TSI) with regard to thyrocyte sensitization and desensitization. The smallest dose of TSH (0·05 mU/ml) capable of stimulating thyroid cells was the same as the minimum dose required to induce desensitization upon subsequent rechallenge with the hormone. In contrast, about 30-fold higher doses of TSI were needed to cause cell refractoriness compared with doses capable of eliciting stimulation. Moreover, significant stimulation of the thyroid with TSI was apparent much later than with TSH. A longer time-lapse was also necessary for TSI to induce densensitization. Likewise, thyrocytes recovered more slowly from TSI compared with TSH desensitization. Although at high doses TSI induced homologous desensitization, at lower doses the antibody, unlike TSH, potentiated the cAMP response to subsequent exposure to the antibody. The stimulatory doses of TSI were in the range usually encountered in active Graves' disease, which may explain why prolonged TSI in vivo sustains a hyperthyroid condition. In addition, we found that under conditions in which TSH leads to desensitization of the cAMP response, the thyroid cells maintained their responsiveness in terms of triiodothyronine secretory activity. Pre-exposure of human thyrocytes to TSI induced heterologous desensitization towards the TSH-stimulated cAMP response. Moreover, addition of the antibody to maximally desensitizing doses of TSH decreased cell sensitivity to the hormone even further. In sharp contrast, preincubation of cells with TSH, or TSH plus TSI, potentiated by four- and twofold respectively the cAMP response to subsequent challenge with TSI. Taken together, the data reveal marked differences between the action of TSH and TSI, and raise interesting questions concerning the mechanism whereby TSH potentiates the cAMP response to TSI.

J. Endocr. (1988) 119, 341–349
Biopotency of highly purified porcine FSH and human LH on gonadal function
Authors: Closset J. , Hennen G.
Published: December 2008

The gonadotrophin preparations that have been used previously to study different aspects of testis function are of limited purity. We have, therefore, purified existing gonadotrophin preparations further. The demonstration of their purity and biological activity are reported as well as their suitability for in-vivo use.

After separation of the subunits of the intact hormones by high-performance liquid chromatography followed by analytical sodium dodecylsulphatepolyacrylamide gel electrolphoresis, no contaminating proteins could be detected in either the FSH or LH preparation. After immunoadsorption, contamination by other pituitary hormones (TSH, prolactin, FSH, LH and GH) was found to be less than 0·002% by weight for all the hormones tested. The biological activity of porcine FSH (pFSH) measured in a Steelman–Pohley assay was 150–170 times more potent than the NIH-FSH-P1 reference preparation. The biopotency of human LH (hLH) in the ovarian ascorbic acid depletion test was measured and appeared to be 8100–8300 IU/mg against the 68/40 International Standard.

The dose-dependent effects of pFSH and hLH on testis weight and the number of FSH and LH receptors were measured in immature (22-day-old) hypophysectomized rats treated for 7 consecutive days. Treatment with FSH induced a dose-dependent increase in testis weight (threefold) when compared with the control. The concentration and total number of LH receptors were increased (two- to sixfold) in a dose-dependent manner. The number of FSH receptors per testis increased while the number of FSH receptors per mg of protein remained unchanged. Administration of human LH to immature hypophysectomized rats had no effect on either LH or FSH receptors, regardless of the dose administered. The plasma concentration of testosterone measured after seven injections of FSH remained at the level of (0·31 nmol/l) found in saline-injected control rats. After 7 days of treatment with hLH, the plasma concentration of testosterone had increased in a dose-dependent manner (three- to tenfold). These results indicate that the gonadotrophin preparations are both highly purified and retained full biological activity and, therefore, are ideal for in-vivo physiological studies.

Journal of Endocrinology (1989) 120, 89–96
Osmotic regulation of hypothalamo-neurointermediate lobe corticotrophin-releasing factor-41 in the rat
Authors: Jessop D. S. , Eckland D. J. A. , Todd K. , Lightman S. L.
Published: December 2008

We have detected significant amounts of corticotrophin-releasing factor-41 (CRF-41) in the rat hypothalamo-neurointermediate lobe system using a radioimmunoassay and reversed-phase high-performance liquid chromatography. Total amounts of CRF-41 in extracts of median eminence (ME), supraoptic nucleus (SON), paraventricular nucleus (PVN) and neurointermediate lobe (NIL) from control animals were 1076 ± 132, 196 ± 44, 22 ± 7 and 147 ± 50 fmol respectively (means ± s.e.m., n = 6). In animals given 340 mmol NaCl/l instead of tap water to drink for 12 days, no significant changes occurred in the CRF-41 content of the ME, SON or PVN, but CRF-41 content increased more than twofold in the NIL (362 ± 58 fmol). Plasma concentrations of CRF-41 and ACTH in control animals were 23 ± 6 and 51 ± 8 pmol/l respectively. After saline treatment no significant change in plasma CRF-41 was detected (20 ± 8 pmol/l) but concentrations of circulating ACTH were decreased (15 ± 2 pmol/l). The CRF-41 content of both the ME and the NIL was significantly depleted after intracerebroventricular injection of colchicine (414 ± 81 and 34 ± 7 fmol respectively). These data suggest that NIL CRF-41 is of hypothalamic origin and can be regulated by an osmotic stimulus.

Journal of Endocrinology (1989) 120, 119–124
Effects of porcine growth hormone and insulin-like growth factor-I (IGF-I) on immunoreactive IGF-binding protein concentration in pigs
Authors: Walton P. E. , Etherton T. D.
Published: December 2008

A specific radioimmunoasay (RIA) was established for an acid-stable insulin-like growth factor-binding protein (IGF-BP) isolated from porcine serum. The RIA recognizes a GH-dependent 150 kDa protein in porcine serum; therefore we postulate that the acid-stable IGF-BP is a component of the high molecular weight IGF-BP in porcine serum.

The IGF-BP concentration was assayed in porcine serum (normal, 2·44 mg/l; hypophysectomized, 0·83 mg/l; serum from a GH-treated pig, 4·72 mg/l), porcine colostrum (2·55 mg/l), milk (0·91 mg/l), and amniotic (1·82–3·14 mg/l), allantoic (2·94–3·58 mg/l) and follicular (2·28 mg/l) fluids.

Serum concentrations of IGF-BP were significantly increased (63%) in pigs chronically injected with porcine GH (pGH) (70 μg/kg body weight per day for 17 days). Concentrations of IGF-BP did not change in porcine serum following acute challenges with pGH (10–1000 μg/kg body weight) or IGF-I (4 or 8 mg per pig).

This is the first report of a specific RIA for the porcine GH-dependent IGF-BP. Our results indicate that this IGF-BP is found in a wide variety of biological fluids and that its concentration appears to be regulated by pGH but not by IGF-I.

Journal of Endocrinology (1989) 120, 153–160
Effects of the new prolactin-producing tumour 7315b on gonadotrophin secretion in adult male and female rats
Authors: Kooy A. , Weber R. F. A. , Ooms M. P. , Vreeburg J. T. M.
Published: December 2008

The effects of the transplantable purely prolactin-secreting tumour 7315b on serum gonadotrophins were studied in adult rats. Possible contributions of the adrenals to the tumour-induced inhibition of serum LH and FSH were evaluated. The suppressive actions of tumour 7315b on serum gonadotrophins in gonadectomized plus adrenalectomized male and female rats were compared.

Within 4 weeks after inoculation of tumour 7315b in intact male rats very high levels of prolactin and decreased serum levels of gonadotrophins and testosterone were recorded. At autopsy reduced weights of testes and accessory sex organs and slightly increased adrenal weights were found. In addition, in animals treated with a small testosterone-filled capsule after castration, tumour 7315b reduced serum concentrations of LH and FSH. Adrenalectomy did not prevent this suppressive action of the tumour on the post-castration rise of serum gonadotrophins. Suppression of serum gonadotrophins during hyperprolactinaemia was greater in gonadectomized plus adrenalectomized female rats than in male rats, indicating that the degree of the tumour-induced suppression of LH and FSH after castration is determined to a large extent by the sex of the animal.

The purely prolactin-secreting tumour 7315b has therefore been shown to be a suitable model for studying the effects of severe hyperprolactinaemia on the pituitary-gonadal axis in rats.

Journal of Endocrinology (1989) 120, 261–268
Adenosine 3',5-cyclic monophosphate phosphodiesterase activity in granulosa cells from Booroola × Romney ewes with and without the F gene
Authors: McNatty K. P. , Heath D. A. , Lun S. , Hudson N. L.
Published: December 2008

Granulosa cells from ovarian follicles (≥ 1 mm diameter) in Booroola ewes which are homozygous (FF) or heterozygous (F+) for the F gene have previously been shown to produce significantly more cAMP in response to FSH or LH than those from similar sized follicles in ewes without the F gene (++). The aim of these studies was to test whether these F gene-specific differences arose because of differences in cAMP-phosphodiesterase (cAMP-PDE) activity.

In the first study using 1 μmol cAMP/1 as substrate, no F gene-specific effects were noted in cAMP-PDE activity in granulosa cells from small (1–2·5 mm diameter, n = 4 per genotype) or large (≥ 3 mm diameter, n = 4 per genotype) follicles from FF, F+ or ++ ewes, despite F gene-specific effects in FSH (1 μg/ml)and LH (0·1 μg/ml)-induced cAMP accumulation in these same cell preparations. The overall mean levels of cAMP-PDE across all genotypes in cells from small and large follicles were 0·47± 0·04 (s.e.m., n = 12) and 0·28 ± 0·03 pmol cAMP/106 cells per min respectively; the mean PDE activity in cells from small follicles was significantly (P < 0·05) higher compared with that in cells from large follicles. In a second study, granulosa cells from each genotype were pooled over all follicle sizes (≥ 1 mm diameter, one pool per genotype) and the rates of cAMP hydrolysis tested over a range of substrate concentrations (0–16 μmol/l) but no genespecific differences with respect to the Michaelis constant and maximum velocity were noted. In a third study, the rates of FSH-induced cAMP accumulation by granulosa cells from small and large follicles of FF and ++ ewes were examined in the presence of a PDE inhibitor, 1-methyl-3-isobutylxanthine (0·2 mmol/l). In this study FSH (1 μg/ml) stimulated significantly more cAMP in cells from FF compared with ++ ewes in both small and large follicles. In cells from small follicles, the mean ± s.e.m. FSHstimulated cAMP levels were 4·7 ± 0·8 (n = 6) for FF ewes and 1·8 ± 0·4 (n = 8) pmol/106 cells per h for ++ ewes (P < 0·025). In large follicles, the cAMP levels were 17·0 ± 3·5 (n = 6) for FF ewes and 6·3 ± 0·5 pmol/106 cells per h for ++ ewes (P < 0·05).

Collectively, these data suggest that the F genespecific difference in cAMP synthesis is probably the result of an event(s) associated with its formation rather than its degradation.

Journal of Endocrinology (1989) 120, 287–293
Age-related variation in circadian rhythms of mitosis in the adrenal cortex of the male rat
Authors: McNicol A. M. , Penman I. D. , Duffy A. E.
Published: December 2008

Using a metaphase arrest technique, mitotic activity was quantified in the adrenal cortex over a 24-h period in 14-day-old male Sprague–Dawley rats before functional rhythmicity of the hypothalamic pituitary-adrenal (HPA) axis is established, and after its onset, in 6- to 7-week-old rats. At all times, proliferative activity was greater in the younger animals, as previously reported. A significant circadian rhythm was identified in both groups, but the timing of the peak differed, lying between 17.00 and 21.00 h at 14 days and 11.00 and 15.00 h at 6–7 weeks. These results raise the possibility that functional rhythmicity of the HPA axis may alter an inherent proliferative rhythm.

Journal of Endocrinology (1989) 120, 307–310
Effects of insulin, glucose and ACTH on corticosterone production by fetal adrenal cells from diabetic rats
Authors: Conliffe P. , Mulay S.
Published: December 2008

Experiments were carried out on Sprague–Dawley rats to determine whether changes in fetal corticosterone levels during maternal diabetes were caused by the accompanying fetal hyperinsulinaemia or fetal hyperglycaemia. Diabetes was induced by injecting streptozotocin (30–45 mg/kg, i.v.) on day 2 of gestation. Fetal adrenals were removed on day 20 of gestation and cultured. Streptozotocin caused moderate (blood glucose 14–22·5 mmol/l) to severe (blood glucose >25 mmol/l) diabetes. Both moderate and severe diabetes caused a decrease in fetal body weights. Relative to non-diabetic controls, maternal and fetal plasma concentrations of corticosterone were higher in the severely and lower in the moderately diabetic rats. Corticosterone production by fetal adrenal cells from control and moderately diabetic rats was comparable, but cells from the severely diabetic animals produced significantly greater amounts of corticosterone than did control cells. Neither glucose (28 mmol/l) nor insulin (1 nmol/l) exerted significant effects on [3H]thymidine uptake or corticosterone production by fetal adrenal cells from non-diabetic, moderately diabetic or severely diabetic rats. Human ACTH (0·02–20 nmol/l) caused a concentration-dependent increase in corticosterone output of comparable magnitude by cells from all three groups of animals. These data suggest that fetal growth abnormalities during diabetic pregnancy are not directly related to changes in glucocorticoid levels and that changes in glucocorticoid levels are not caused by any direct action of fetal hyperinsulinaemia or hyperglycaemia on adrenal cells.

Journal of Endocrinology (1989) 120, 393–399
High-density lipoproteins (HDL) stimulate placental lactogen secretion in pregnant ewes: further evidence for a role of HDL in placental lactogen secretion during pregnancy
Authors: Grandis A. , Jorgensen V. , Kodack L. , Quarfordt S. , Handwerger S.
Published: December 2008

Previous studies from our laboratory showed that high-density lipoproteins (HDL) stimulate the release of human placental lactogen (PL) from cultured trophoblast cells from normal pregnant women. To determine whether HDL stimulates PL secretion in vivo, ovine HDL was infused over 2–5 min into 11 pregnant ewes (22 separate experiments) at 86–130 days of gestation via an indwelling catheter into the maternal jugular vein. The HDL, freshly prepared from the plasma of pregnant ewes by differential flotation ultracentrifugation, was greater than 99% purified as judged by SDS-PAGE. Plasma samples were obtained from the ewes before and at 0·5-h intervals for 6 h following the infusions and were assayed for PL by a specific homologous radioimmunoassay. The maternal infusion of HDL at doses of 302–784 mg (5·3–13·8 mg/kg body weight) stimulated significant increases in maternal plasma PL concentrations in six out of eight experiments (six ewes), and the infusion of 108–264 mg (1·9–4·6 mg/kg) stimulated plasma PL concentrations in two out of six experiments. In contrast, HDL at doses < 100 mg were without effect in eight experiments. The response to the HDL infusions was characterized by a sustained increase in plasma PL concentrations beginning 1·5–2·5 h after the infusions, reaching a maximum 274·2 ± 21·9% of the baseline value (P<0·001). In contrast, the maternal infusion of lipoprotein-free plasma proteins or saline had no effect on maternal plasma PL concentrations. Although the infusion of HDL into pregnant ewes stimulated an increase in maternal plasma PL concentrations, the infusion of HDL (0·8–22·0 mg/kg) into three fetuses in seven separate experiments had no effect on fetal plasma PL concentrations. The demonstration that HDL stimulates an increase in plasma PL concentrations in pregnant ewes strongly supports a novel physiological role for HDL in the regulation of PL secretion.

Journal of Endocrinology (1989) 120, 423–427
Peptides related to α-melanocyte-stimulating hormone are commonly produced by human pituitary corticotroph adenomas: no relationship with pars intermedia origin
Authors: Coates P. J. , Doniach I. , Wells C. , Hale A. C. , Rees L. H. , Besser G. M.
Published: December 2008

The presence of immunoreactive (ir)-α-MSH has been investigated by immunocytochemistry in 24 pituitary adenomas and one case of corticotroph hyperplasia causing Cushing's disease, in four adenomas causing Nelson's syndrome, and in ten 'silent' corticotroph adenomas. It was found that a high proportion of these adenomas have a population of cells containing ir-α-MSH in addition to ir-ACTH. In some instances, these adenomas were clearly not associated with the residual intermediate lobe of the pituitary. Radioimmunoassay of plasma from patients with Cushing's disease or Nelson's syndrome showed elevated levels of ir-α-MSH in the majority of cases. Characterization of the ir-α-MSH in adenoma cells by immunocytochemistry, using an antiserum selective for acetylated forms of α-MSH, suggested that only the desacetyl form was present in each case examined. High-performance liquid chromatography of adenoma tissue extracts revealed material co-eluting with acetylated forms of α-MSH in only one of six cases. These results have been compared with corticotroph adenomas in animal pituitary glands, and it is concluded that the presence of α-MSH peptides cannot be used as a marker for intermediate lobe tumours, and that desacetyl α-MSH is commonly produced by corticotroph adenomas.

Journal of Endocrinology (1989) 120, 531–536
In-vivo effect of ethanol on release of LH-releasing hormone and LH in rats
Authors: Emanuele M. A. , Tentler J. , Reda D. , Kirsteins L. , Emanuele N. V. , Lawrence A. M.
Published: December 2008

The effect of exposure to ethanol on hypothalamic LH-releasing hormone (LHRH) release in vivo was investigated in rats both acutely (i.p. injection) and after 3 days of administration, utilizing a permanent gastric cannula. In both designs, the animals were castrated before being given ethanol and, in both experiments, ethanol successfully lowered the post-castration LH rise compared with control castrated animals. In both the acutely and chronically treated groups, basal LHRH release was not impaired, despite the documented decrease in LH levels. Finally, stimulated LHRH release was investigated with depolarizing concentrations of potassium and, again, no change was noted between the hypothalamic release of this decapeptide in the ethanol-exposed compared with the ethanol-naive animals. Thus, ethanol failed to inhibit basal or stimulated LHRH secretion in the acutely and chronically treated animal. This lack of effect on LHRH occurred despite a concomitant lowering of serum concentrations of LH.

Journal of Endocrinology (1989) 121, 37–41
Plasma concentrations of cholecystokinin octapeptide and food intake in male rats treated with cholecystokinin octapeptide
Authors: Lindén A. , Uvnäs-Moberg K. , Forsberg G. , Bednar I. , Södersten P.
Published: December 2008

Intraperitoneal injection of 5 μg cholecystokinin octapeptide (CCK-8) into male rats deprived of food for 48 h produced a transient (less than 15 min) increase in plasma levels of CCK-8 but suppressed food intake for an extended period (45 min). Plasma concentrations of CCK-8 after i.p. injection of CCK-8 were raised to levels which were fairly comparable to those after feeding. Intracerebroventricular (i.c.v.) injection of the CCK antagonist proglumide (100 μg) reversed the effect of CCK-8 on food intake, while i.p. injection of proglumide (100 μg) did not have this effect. Feeding increased the plasma concentrations of somatostatin and gastrin but not of oxytocin, and somatostatin and oxytocin but not gastrin were released in response to i.p. injection of CCK-8. However, neither somatostatin nor oxytocin affected food intake, and their release in response to CCK-8 was unaffected by i.c.v. injection of proglumide. These results support the suggestion that CCK-8 is a physiological 'satiety' peptide, which can affect food intake in rats by mechanisms involving both peripheral and central CCK receptors.

Journal of Endocrinology (1989) 121, 59–65