bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification by flow cytometry of the prostaglandin-producing cell populations of term human decidua
Authors: Norwitz E. R. , Starkey P. M. , Bernal A. López , Turnbull A. C.
Published: December 2008

Human term decidua produces prostaglandins (PGs) which have been implicated in the initiation of human parturition. Using flow cytometry to isolate pure cell populations, we have investigated the cell types responsible for decidual PG production. Cell dispersions were prepared enzymatically from decidua vera isolated from term placentae, and were incubated in Dulbecco's Modified Eagle's Medium containing 0·25% bovine serum albumin at 37 °C. PGF2α and PGE2 output were measured by radioimmunoassay of the conditioned medium. Production of PGF2α (fmol/106 cells per 3 h) exceeded that of PGE2 at 273 (108–322) 322) versus 97 (38–127) respectively (median (range)). The decidual cell dispersions were then incubated with monoclonal antibodies (anti-CD45 which labels the leukocyte common antigen or anti-human leukocyte antigen class II (HLA-DR) which is specific for macrophages in this tissue) and sorted by flow cytometry. The resultant antibody-positive and -negative cell populations were incubated and PG production was measured. Controls showed that antibody labelling and sorting did not alter PG production. PGF2α and PGE2 output by bone marrow-derived (CD45-positive) cell populations exceeded that of non-bone marrow-derived (CD45-negative) cells. Furthermore, we were able to demonstrate that the HLA-DR-positive macrophage population had the highest PGF2α and PGE2 production rates in human term decidua in vitro.

Journal of Endocrinology (1991) 131, 327–334
Prostaglandin E2 enhances AVP-stimulated but not CRF-stimulated ACTH secretion from cultured fetal sheep pituitary cells
Authors: Brooks A. N. , Gibson F.
Published: December 2008

This study examined the ability of prostaglandin E2 (PGE2) to regulate ACTH secretion from cultured anterior pituitary cells of fetal sheep between days 130 and 140 of gestation (term = 145 days). Corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) induced dose-dependent (0·1–1000 nmol/l) increases in ACTH secretion from fetal sheep pituitary cells maintained in culture for 6 days, with AVP being significantly (P<0·01) more potent than CRF. PGE2 (1000 nmol/l) significantly (P<0·05) enhanced the ability of AVP, but not CRF, to stimulate ACTH secretion. However, PGE2 given alone (0·1–1000 nmol/l) had no effect on ACTH secretion. Concomitant administration of CRF and AVP induced a greater release of ACTH than after treatment with either peptide alone, a synergistic interaction which was unaffected by simultaneous administration of PGE2.

These results provide evidence for a direct action of PGE2 on ACTH secretion from the fetal sheep pituitary gland via a specific interaction with AVP. This interaction may allow increased fetal plasma concentrations of PGE2, seen during late gestation, to stimulate fetal pituitary–adrenal maturation.

Journal of Endocrinology (1992) 132, 33–38
Effects of cytokines on rat insulinoma INS-1 cells
Authors: Janjic D. , Asfari M.
Published: December 2008

To investigate further the role of cytokines in the pathogenesis of type I insulin-dependent diabetes mellitus, the effects of interleukin-1β (IL-1), tumour necrosis factor-α (TNF) and γ-interferon (IFN) were tested on rat insulinoma INS-1 cells. Whereas TNF and IFN had, respectively, a minor or no effect on insulin production, IL-1 caused a time- and dose-dependent decrease in insulin release and lowered the insulin content as well as the preproinsulin mRNA content of INS-1 cells. Both IL-1 and TNF exerted a cytostatic effect, estimated by a decrease in [3H]thymidine incorporation, while only IL-1 decreased cell viability as measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test.

The glutathione content of INS-1 cells was shown to be modulated by the presence of 2-mercaptoethanol in the culture medium, but was not affected by IL-1 or TNF.

In conclusion, INS-1 cell culture is considered to be a useful model for studying the effect of cytokines on insulin-producing cells. The differentiated features of these cells will permit several questions to be addressed regarding the mechanism of action of IL-1 and eventually other cytokines, both at the level of gene expression and of intracellular signalling.

Journal of Endocrinology (1992) 132, 67–76
The thyrotrophin-releasing hormone (TRH)-like peptides in rat prostate are not formed by expression of the TRH gene but are suppressed by thyroid hormone
Authors: Bilek R. , Gkonos P. J. , Tavianini M. A. , Smyth D. G. , Roos B. A.
Published: December 2008

Thyrotrophin-releasing hormone (TRH)-immunoreactive peptides were extracted from rat prostate and divided into two groups by mini-column cation exchange chromatography. The amounts of the peptides in each group were determined by radioimmunoassay with a TRH antiserum. The unretained peptides which lacked a basic group and the retained peptides which possessed a basic group were further purified by high-performance liquid chromatography. The unretained fraction was found to contain a series of TRH-immunoreactive peptides, one of which corresponded chromatographically to synthetic pGlu-Glu-Pro amide and another to pGlu-Phe-Pro amide. None of the TRH-immunoreactive peptides in either fraction exhibited the chromatographic behaviour of TRH. Additional evidence for the absence of TRH gene expression in the prostate was obtained by Northern blot analysis and by application of polymerase chain reaction amplification, which failed to reveal TRH mRNA. Furthermore the preproTRH-derived peptide, preproTRH(53–74), could not be detected by radioimmunoassay.

The influence of thyroid status was investigated on the levels of the TRH-like peptides in the prostate. Adult rats were treated chronically with thyroxine (T4) or propylthiouracil (PTU) and the concentrations of the TRH-immunoreactive peptides were determined by chromatography and radioimmunoassay. Treatment with T4 caused the levels of the neutral and acidic TRH-like peptides to fall to approximately one-third of the levels in the controls. No significant difference from the controls was seen in the concentrations of the peptides in the prostates of rats rendered hypothyroid by administration of PTU.

The results demonstrate that rat prostate contains TRH-immunoreactive peptides which are not derived from the TRH gene. It is concluded that the TRH-like peptides arise from one or more genes which are structurally distinct from that which codes for the TRH preprohormone. Since these peptides are amidated and their levels are sensitive to hormone administration, it is likely that they fulfil a biological function.

Journal of Endocrinology (1992) 132, 177–184
Effect of growth hormone treatment on the distribution of insulin-like growth factor-I between plasma and lymph of lactating sheep
Authors: Davis S. R. , Hodgkinson S. C. , Prosser C. G. , Gluckman P. D. , Buonomo F. C. , Collier R. J.
Published: December 2008

Plasma and mammary efferent lymph concentrations of insulin-like growth factor I (IGF-I) were determined in lactating ewes before and after treatment with GH (10 mg/day) for 3 days. The lymph:plasma ratio of IGF-I increased from 0·34 to 0·47 after GH treatment when the IGF-I content of plasma increased by 19·4 nmol/l (from 32·1 nmol/l) and lymph by 13·7 nmol/l (from 10·7 nmol/l). This increase in the relative content of IGF-I in lymph was associated with increased lymph content of IGF-I in a lower molecular mass pool (nominally 50 kDa) derived by size exclusion chromatography.

GH treatment increased the total binding capacity for IGF-I in both high (150 kDa) and low (50 kDa) molecular mass pools of plasma and the 150 kDa pool in lymph but there was a proportionally greater increase in 50 kDa total binding in lymph relative to plasma. Further, GH treatment increased the 'saturation' of the 50 kDa binding proteins but decreased the 'saturation' of the 150 kDa fraction, in both plasma and lymph.

Ligand blot analysis of IGF-binding proteins (IGFBPs) in plasma and lymph showed that GH treatment of lactating sheep increased IGFBP-3 and decreased IGFBP-2 in plasma and lymph. Radioimmunoassay of IGFBP-2 showed that while GH treatment reduced the plasma content of IGFBP-2 by about half, the lymph:plasma ratio was increased from 0·68 to 0·87.

GH treatment of lactating ewes not only increased the IGF-I content of plasma but increased the apparent efficiency of transfer of IGF-I across capillary endothelium to mammary efferent lymph.

Journal of Endocrinology (1992) 132, 339–344
Regional and cellular distribution within the rat prostate of two mRNA species undergoing opposite regulation by androgens
Authors: Bettuzzi S. , Zoli M. , Ferraguti F. , Ingletti M. C. , Agnati L. F. , Corti A.
Published: December 2008

We have investigated, by in-situ hybridization histochemistry, the distribution within the rat ventral prostate of the mRNAs for sulphated glycoprotein-2 (SGP-2) and ornithine decarboxylase (ODC; EC 4.1.1.17), two proteins that appear to be inversely regulated by androgens in this organ, in that the level of SGP-2 mRNA is lowered, while the activity of ODC is enhanced by the latter hormones. Low-magnification autoradiograms of whole ventral prostate sections showed that, in intact animals, the SGP-2 transcript was only detectable in restricted areas and not diffused evenly throughout the section. Reciprocally, the ODC transcript was not detectable in areas where the SGP-2 transcript was detected, but appeared distributed uniformly in the remaining parts of the section. The effect of castration on the levels of the two mRNAs was evaluated by a semiquantitative analysis of autoradiograms from whole ventral prostate sections using an autoimmune image analyser. Four days after castration, SGP-2 mRNA increased by about 11-fold, while ODC mRNA decreased by fivefold. The distribution of the two mRNAs among the different cell types, studied by treating the slides with photographic emulsion and counterstaining, showed that both were expressed exclusively in the epithelial luminal cells of the ducts. Furthermore, each of the two mRNAs preferentially accumulated in a cell population which was morphologically distinct while accumulation of the other was negligible. SGP-2 mRNA was mostly found in cuboidal epithelial cells and ODC mRNA in columnar epithelial cells. Castration caused a dramatic accumulation of SGP-2 and a decrease in ODC mRNAs in the cells of the columnar epithelium 4 days later. These data suggest that, in the ventral prostate of intact animals, SGP-2 is expressed in the proximal ducts whose luminal epithelium consists of cuboidal cells undergoing apoptotic phenomena and not in the intermediate and distal ducts characterized by columnar epithelia with active protein synthesis and cell multiplication. In the intermediate and distal parts of the ductal system the ODC gene would be expressed at a high rate while being turned off in the proximal ducts. Castration, resulting in apoptosis of the epithelial cells of the intermediate and distal ducts, caused SGP-2 to be actively expressed and ODC to be repressed in the latter segments.

Journal of Endocrinology (1992) 132, 361–367
Epidermal growth factor alters milk composition and fluid balance of lactating ewes
Authors: Gow C. B. , Moore G. P. M.
Published: December 2008

Lactating ewes were treated with murine epidermal growth factor (EGF) and its effects on concomitant milk production and composition were observed. Six ewes were infused via the jugular vein with 200 ml saline/day over 4 days (days 9–12 of lactation) followed by EGF at a dose rate of 0·5 mg/day in 200 ml saline over 4 days (days 13–16). All ewes then received a further infusion of 200 ml saline/day over 4 days (days 17–20). During the experiment a maintenance (lactation) diet was offered and ewes were machine-milked twice daily.

An EGF-immunoreactive material was detected in mammary secretions and urine throughout the experiment, but only in plasma (1–9 μg/l) during the period of EGF infusion. The amount of EGF appearing in milk and urine increased from 37 μg and 10 μg respectively (day 1 of EGF infusion) to 56 μg and 17 μg respectively (day 4). EGF treatment resulted in lower milk yield and reduced concentration of lactose and protein; milk fat concentration fell after EGF infusion had ceased. Water intake increased markedly during EGF infusion and was 60% (4 kg) greater on day 4 than that measured during the first saline infusion. Urine volume also increased and was 164% (3·6 kg) greater by day 4 of EGF infusion compared with that recorded in the first saline infusion. Water retention (intake minus output in milk, urine and faeces) was significantly higher on the day after EGF infusion ceased than that found during the first saline infusion. The possibilities that the increased water intake was primary, or secondary, to a diuretic effect of EGF are discussed.

Journal of Endocrinology (1992) 132, 377–385
Puberty in birds: the reproductive system of starlings does not respond to short days until birds are fully grown
Authors: McNaughton F. J. , Dawson A. , Goldsmith A. R.
Published: December 2008

If adult starlings are kept on long days, they rapidly become refractory to long days (photorefractory). The recovery of the ability to respond to long days (photosensitivity) occurs after transfer to short days. Photosensitivity is associated with an increase in hypothalamic content of gonadotrophin-releasing hormone (GnRH), and, in castrated birds, with an increase in plasma LH. If photorefractory adult or juvenile starlings are transferred to short days, these events begin 3 and 4 weeks respectively after transfer. Starlings apparently hatch in a photorefractory state. However, if nestlings are hand-reared under short days, the increases in GnRH and LH begin at 6 and 7 weeks of age respectively. Is this 3-week delay, which corresponds to the time to reach adult body size, simply due to a slower response, or are nestlings incapable of responding to short days until fully grown? Castrated male nestling starlings were hand-reared under short days, under long days or under long days initially and transferred to short days at 2, 3, 6 or 9·5 weeks of age. The increase in plasma LH in birds transferred to short days at or before 3 weeks began at the same time as in birds kept on short days (7 weeks). In birds transferred at 3 weeks or later, the increase in LH began 4 weeks after transfer, irrespective of age. Intact female starlings showed similar responses. Birds kept on short days did not moult whereas birds transferred from long days to short days at 3 weeks did. These results suggest that nestlings are capable of perceiving daylength, but that the GnRH neurosecretory system does not respond to short days until birds are fully grown.

Journal of Endocrinology (1992) 132, 411–417
Possible involvement of glucocorticoids in the reduction of serum insulin levels by interleukin-1 in the rat
Authors: Shimizu H. , Uehara Y. , Tanaka Y. , Shimomura Y. , Kobayashi I.
Published: December 2008

Evidence is accumulating that adrenal steroids may be involved in the metabolic effects of cytokines. We evaluated the possible involvement of glucocorticoids in the inhibition of pancreatic insulin secretion by interleukin-1β (IL-1β), one of the cytokines produced by inflammatory cells. In the first group of experiments, adrenalectomized rats showed a significant reduction in basal and glucose (0·5 g/kg, i.v.)-stimulated immunoreactive insulin (IRI) levels after injection of IL-1β (1·0 μg/kg), but intact rats did not. Pretreatment with IL-1β increased plasma glucose levels 2 and 15 min after an i.v. bolus of glucose in adrenalectomized rats. In the second group of experiments, dexamethasone supplement (0·1 mg/kg) given to adrenalectomized rats cancelled the reduction in plasma glucose levels by IL-1β, and rats treated with 1·0 mg dexamethasone/kg showed a significant increase in basal IRI levels and enhanced serum IRI levels after IL-1β injection. However, 1·0 mg deoxycorticosterone/kg given daily for 7 days failed to cancel the effect of IL-1β on the reduction of serum IRI levels, although it attenuated the weight loss after adrenalectomy. The data suggested that withdrawal of glucocorticoids after adrenalectomy potentiates the effect of IL-1β on the reduction of serum IRI levels. Glucocorticoids may have a protective action against the reduction of serum IRI levels by IL-1β.

Journal of Endocrinology (1992) 132, 419–423
The glucocorticoid antagonist mifepristone reveals abnormal regulation of the adrenocortical system in obese Zucker rats
Authors: Pesonen U. , Koulu M. , Heikinheimo O. , Huupponen R.
Published: December 2008

The effects of the potent glucocorticoid type-II receptor (GR) antagonist, mifepristone, on corticosterone secretion and on expression of preprocorticotrophin-releasing factor (preproCRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and of pro-opiomelanocortin (POMC) mRNA in the pituitary gland were investigated in lean and obese Zucker rats. Treatment with mifepristone for 4 days (10 mg/kg orally twice daily) significantly (P < 0·05) stimulated corticosterone secretion in lean but not in obese rats. In lean rats the enhanced corticosterone secretion was associated with non-significant increments in the expression of preproCRF mRNA in the PVN and of POMC mRNA in the pituitary gland, while mifepristone significantly (P < 0·05) reduced the expression of preproCRF mRNA in the PVN of obese Zucker rats. It is concluded that antagonism of GR by mifepristone results in persistent activation of the adrenocortical axis in lean Zucker rats due to blockade of feedback inhibition by circulating corticosterone. In obese animals the abnormal response to mifepristone suggests that the neuroendocrine control of the HPA axis is altered in genetically determined obesity.

Journal of Endocrinology (1992) 132, 425–431
Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I
Authors: Slootweg M. C. , Most W. W. , van Beek E. , Schot L. P. C. , Papapoulos S. E. , Löwik C. W. G. M.
Published: December 2008

Insulin-like growth factor-I (IGF-I) is a potent stimulator of bone formation. Whether this growth factor also induces bone resorption has not been studied in detail. We used two organ culture systems to examine the direct effect of IGF-I on bone resorption. Fetal mouse radii/ulnae, containing mature osteoclasts, showed no response to IGF-I, indicating that osteoclastic activity is not influenced by IGF-I. Fetal mouse metacarpals/metatarsals, containing just osteoclast precursors and progenitors, showed an increase in resorption in response to IGF-I, indicating that IGF-I stimulates the formulation of osteoclast precursors/progenitors and thereby increases the number of osteoclasts.

Interleukin-6 (IL-6) has been hypothesized to be a mediator of bone resorptive agents such as parathyroid hormone (PTH). Both radii/ulnae and metacarpals/metatarsals reacted to IGF-I with an increase in IL-6 production. IL-6 production by UMR-106 osteogenic osteosarcoma cells was positively modulated by IGF-I, indicating that osteoblasts are likely to be the cells responsible for increased IL-6 production by the bones, and that IL-6 might be a mediatory of IGF-I-stimulated bone resorption.

Journal of Endocrinology (1992) 132, 433–438
Further characterization of the steroidogenic responsiveness of purified zona fasciculata/reticularis cells from bovine adrenal cortex before and after primary culture: changing responsiveness to phosphoinositidase C agonists
Authors: Bird I. M. , Clyne C. D. , Lightly E. R. T. , Williams B. C. , Walker S. W.
Published: December 2008

When bovine adrenocortical cells from the zona fasciculata/reticularis (zfr) are maintained in primary culture, cortisol secretion in response to acute stimulation with ACTH and adrenaline (which activate adenylate cyclase) is seen to increase steadily over the first 48 h, while secretion in response to angiotensin II and acetylcholine (which activate phosphoinositidase C) shows an initial decline in the first 24 h and a recovery to maximum after 48 h. We have investigated whether these discrepant changes in cortisol secretory response to the different agonists are due to changes in formation of the associated second messengers (cAMP or inositol phosphates), or altered coupling of these second messenger signals to steroid secretion.

Increases in steroid secretion in response to ACTH and adrenaline were paralleled by increased cAMP. Steroid secretion in response to exogenous 8-bromoadenosine 3′:5′-cyclic monophosphate also increased steadily during this 48-h period. Thus increased responsiveness was due to both increased second messenger formation and increased coupling to the steroid secretory response.

The decreased steroid secretory response to angiotensin and acetylcholine after 24 h, and subsequent recovery after 48 h in culture, were accompanied by an increased formation of phosphoinositols after 24 h and a further increase by 48 h. However, the steroid secretory response to a combination of calcium ionophore and the protein kinase C activator, phorbol 12-myristate 13-acetate, was reduced after 24 h and recovered by 48 h of culture. Fura-2-loaded cells also showed an increase in intracellular [Ca2+] after 24 h in culture. Thus the impaired steroid secretory response to angiotensin II and acetylcholine after 24 h of culture was not due to reduced formation of second messengers but to a failure of Ca2+ and diacylglycerol so formed to activate the steroid secretory process.

Reversible uncoupling of the steroid secretory response from the Ca2+- and diacylglycerol-based but not the cAMP-based second messengers observed in bovine zfr cells suggests that differential control of steroid secretion and other cell functions may be possible in vivo for activators of phosphoinositidase C, and may explain apparently discrepant results from studies on other in-vitro adrenocortical cell preparations.

Journal of Endocrinology (1992) 133, 21–28
Effect of administration of growth hormone on plasma and intracellular levels of thyroxine and tri-iodothyronine in thyroidectomized thyroxine-treated rats
Authors: Geelhoed-Duijvestijn P. H. L. M. , Roelfsema F. , Schröder-van der Elst J. P. , van Doorn J. , van der Heide D.
Published: December 2008

We have studied the effects of the administration of GH on plasma levels and peripheral production of tri-iodothyronine (T3) from thyroxine (T4) in thyroidectomized male Wistar rats given a continuous i.v. infusion of T4 (1 μg/100 g body weight per day) and GH (120 μg per day) for 3 weeks. Tracer doses of 131I-labelled T3 and 125I-labelled T4 were added to the infusion. At isotopic equilibrium (10 days after the addition of 125I-labelled T4) the rats were bled and perfused.

The plasma appearance rate for T3 was higher (10·6±1·3 vs 8·4 ± 2·8 pmol/h per 100 g body weight, P = 0·05) and plasma TSH was lower (246±24 vs 470±135 pmol/l, P<0·01) in GH-treated rats. The amount of T3 in liver (12·3 ±2·8 vs 5·5 ± 1·7 pmol/g wet weight, P<0·01), kidney (11·5±1·4 vs 6·5± 1·4 pmol/g wet weight, P <0·01) and pituitary (8·8 ±2·7 vs 4·8±0·5 pmol/g wet weight, P< 0·01) was higher than in controls, mainly as a result of an increased local production of T3 from T4, but plasma-derived T3 was also higher in most organs.

We found an increased intracellular T3 concentration in the pituitary which may be responsible for the lower plasma TSH concentration in the GH-treated rats. Since the increase in locally produced T3 is found particularly in liver, kidney and pituitary, typical organs that express 5′-deiodinase activity, we suggest that GH acts on thyroid hormone metabolism by stimulating type-I deiodinase activity.

Journal of Endocrinology (1992) 133, 45–49
Kinetics of placental lactogen in mid- and late-gestation ovine fetuses
Authors: Schoknecht P. A. , Currie W. B. , Bell A. W.
Published: December 2008

Placental lactogen (PL) is found in fetal plasma throughout gestation, and PL receptors occur on many types of fetal cells. In this study, the entry rate of PL into the fetal circulation was estimated by injection of 125I-labelled ovine PL into two mid- and four late-gestation fetuses. At both ages, PL appears to be distributed into two body pools. One pool has a rapid half-life (approximately 9 min) and a volume of distribution approximately 8% of body weight, while the second pool has a longer half-life (approximately 45 min) and a distribution volume only 4% of body weight. The first pool is presumably blood plasma, but the physiological identity of the second pool is unknown. The effective half-life of PL is approximately 15 min, and the liver is suggested as a probable major site of degradation. These estimates were confirmed in late gestation by measuring fetal plasma concentrations of PL in response to a continuous infusion of unlabelled PL. The kinetic parameters estimated in this study can be used to determine the quantity of exogenous hormone required to alter PL concentration in fetal plasma in a predictable manner.

Journal of Endocrinology (1992) 133, 95–100
Cultured dermal papilla cells from androgen-dependent human hair follicles (e.g. beard) contain more androgen receptors than those from non-balding areas of scalp
Authors: Randall V. A. , Thornton M. J. , Messenger A. G.
Published: December 2008

Androgens stimulate hair growth in many areas, e.g. the beard; they also induce regression and balding on the scalp with increasing age in genetically disposed individuals. The cause(s) of this biological conundrum is unknown but age-related; androgen-potentiated changes also occur in the prostate. The mesenchymederived dermal papilla situated at the base of the hair follicle is thought to play an important role in regulating the growth and development of the follicular epithelium. Since androgens probably act on the hair follicle via the dermal papilla, cultures of dermal papilla cells from human hair follicles with differing responses to androgens in vivo have been established and their ability to bind androgens assessed. Receptor binding was assayed by saturation analysis (0·05–10 nmol/l) using the synthetic non-metabolizable androgen, [3H]mibolerone. Shionogi 115 cells were also assayed as a positive control.

Specific high-affinity low-capacity androgen receptors were identified in 12 dermal papilla primary cell lines with similar characteristics to established androgen receptors. Cells from androgen-sensitive follicles (beard, scrotum and pubis) contained higher levels of androgen receptors than those derived from relatively androgeninsensitive non-balding scalp follicles whether the receptor content was calculated in relation to cell number, protein or DNA content of the cells. These results support the hypothesis that androgens act on hair follicles via the dermal papilla in vivo and demonstrate that dermal papilla cells exhibit an altered phenotype in culture which depends on the body site from which they were derived. Cultured human dermal papilla cells should prove a useful model system for studies of the mechanism of androgen action, and further investigations may elucidate the paradox of why bald men can grow beards.

Journal of Endocrinology (1992) 133, 141–147
Vitamin A deficiency and glucocorticoid receptor activity in rat liver
Authors: Audouin I. , Garcin H. , Pailler-Rodde I. , Higueret P.
Published: December 2008

The influence of vitamin A on the binding properties of hepatic glucocorticoid receptors (GR) was studied in young rats 7 weeks after they had been given a diet with or without vitamin A. Scatchard analysis showed an increased capacity of cytosolic GRs to bind dexamethasone in vitamin A deficiency. In these rats, an increase in tyrosine aminotransferase also occurred, and this could be related to the increased formation of hormone–GR complexes. Measurement of protein kinase C activity showed an increase which might be related to the functional activity of GRs.

Journal of Endocrinology (1992) 133, 169–173
A comparative analysis of the neuroendocrine mechanisms regulating ovulation, affected by a unilateral implant of atropine in the preoptic-anterior hypothalamic area, in intact and hemiovariectomized adult rats
Authors: Cruz M. E. , Castro J. , Domínguez R.
Published: December 2008

The effects were analysed of a unilateral implant of atropine on ovulation in intact and hemiovariectomized adult rats, together with the response of the atropine-implanted rats to hormone replacement. An outer cannula directed to the left or right preoptic (POA)-anterior-hypothalamic area (AHA) was implanted into cyclic adult rats. A group of animals in oestrus was hemiovariectomized and some were also implanted with a cannula. After two consecutive 4-day cycles, the hemiovariectomized animals were implanted with atropine (23 ± 4 μg) or cholesterol (25 ± 2 μg) on the day of oestrus. Atropine implanted into the left side of the POA-AHA blocked ovulation and compensatory ovarian hypertrophy, whilst implants in the right side had no effects. Administration of gonadotrophin-releasing hormone (GnRH; 3·7 μg/kg) at 13.00 h on the expected day of pro-oestrus induced ovulation in six out of seven treated animals. Of 19 rats with an implant of atropine in the left side of the POA-AHA, one ovulated after treatment with pregnant mare serum gonadotrophin (PMSG) on oestrus, or oestradiol benzoate or human chorionic gonadotrophin (hCG) on day 2 of dioestrus. The effects on ovulation of a unilateral implant of atropine into the POA-AHA of cyclic adult rats and the responses of such rats to GnRH, PMSG, hCG and oestradiol benzoate replacement were also studied. Ovulation was induced in rats with a unilateral implant of atropine and which had been treated with GnRH or hCG at 13.00 h on the expected day of pro-oestrus after the implant. In rats with an atropine implant, treatment with PMSG on the day of implantation or with oestradiol benzoate on day 2 of dioestrus restored ovulation in those with the implant in the left side of the hypothalamus, but was ineffective in those with the implant in the right side. The results suggested that in the adult rat the muscarinic mechanisms regulating preovulatory GnRH release, as well as the stimulatory effects of oestrogen, are lateralized. As the results observed in intact and hemiovariectomized animals subjected to the same treatments were different, it was concluded that the cholinergic neuroendocrine mechanisms regulating ovulation are related to the neural information arising from the ovaries and reaching the POA-AHA.

Journal of Endocrinology (1992) 133, 205–210
Effect of decapitation and chronic in-vivo treatment with a gonadotrophin-releasing hormone agonist on testicular steroidogenesis in the rat fetus
Authors: Habert R.
Published: December 2008

To study the effect of in-vivo gonadotrophin-releasing hormone (GnRH) treatment on testicular testosterone production during late fetal life in the rat, 18·5-, or 20·5-day-old fetuses were decapitated and injected with either long-acting microcapsules containing the GnRH agonist d-Trp-6-GnRH or vehicle only. Two days later, fetal and maternal plasma was collected and fetal testes were removed and incubated for 6 h in medium with either 100 ng LH/ml or without LH. The GnRH agonist concentrations in the plasma of GnRH-treated decapitated male fetuses were comparable in the two age-related groups (5 nmol/l). After treatment of the fetus with d-Trp-6-GnRH, the agonist was recovered in maternal plasma, showing that this peptide can cross the fetal–maternal barrier. In 22·5-day-old decapitated vehicle-treated male fetuses, the plasma testosterone level dropped to that observed in control female fetuses, and treatment of decapitated male fetuses with the GnRH agonist did not further reduce it. At both days 20·5 and 22·5, basal in-vitro testosterone secretion by testes from decapitated vehicle-treated fetuses was lower than secretion by testes from intact control fetuses from the same litter, but LH-stimulated secretion was similar in both groups. Both basal and LH-stimulated secretion by testes from GnRH-treated decapitated fetuses was lower than secretion by testes from vehicle-treated decapitated fetuses and larger reductions were measured on day 22·5 than on day 20·5 (−48 vs −18% for basal secretion, and −76 vs −40% for LH-stimulated secretion).

These results suggest that, in contrast to immature Leydig cells, fetal Leydig cells are not desensitized to gonadotrophic stimulation after hypophysial deprivation, and that, in the rat, a negative testicular response to a putative intratesticular GnRH or to some other factor using the same intracellular pathway is established during late fetal life.

Journal of Endocrinology (1992) 133, 245–251
α-Melanocyte-stimulating hormone stimulates protein kinase C activity in murine B16 melanoma
Authors: Buffey J. , Thody A. J. , Bleehen S. S. , Neil S. Mac
Published: December 2008

The effect of α-melanocyte-stimulating hormone (α-MSH) on protein kinase C activity and distribution was investigated in murine B16 F1 melanoma cells, α-MSH was found to induce an increased association of protein kinase C (PKC) activity with the particulate fraction of the cells, with an associated loss of enzyme activity from the soluble fraction. The peak response to α-MSH occurred between 20 and 60 min of incubation time, and enzyme activities redistributed to those seen in the control cells over the following 12 to 24 h. The average response to α-MSH (1 nmol/l) was an approximate 2·5-fold increase in the percentage of enzyme activity associated with the membrane within 1 h of exposure to α-MSH; the particulate enzyme activity represented 19·2 ± 4·4% of total activity in the absence of α-MSH and 50·7 ± 4·7% (means ± s.e.m., n = 9, P < 0·005) in the presence of α-MSH (1 nmol/l). Cells which had a relatively small percentage of their PKC activity on the membrane initially were significantly (P < 0·01) more responsive to α-MSH stimulation than cells which initially had a relatively large percentage of PKC activity on the membrane. The association of PKC activity with the membrane showed some evidence of being dose-related to α-MSH. This is the first report, to the best of our knowledge, of α-MSH activating PKC.

Journal of Endocrinology (1992) 133, 333–340
Immunoneutralization and immunocytochemical localization of inhibin α subunit during the mid-luteal phase in the stump-tailed macaque
Authors: Fraser H. M. , Smith K. B. , Lunn S. F. , Cowen G. M. , Morris K. , McNeilly A. S.
Published: December 2008

The putative endocrine role of inhibin in the control of FSH secretion during the luteal phase in the primate was investigated by immunoneutralization. Antisera against the 1–23 amino acid sequence of the N-terminus of the human inhibin α subunit were raised in a ewe and three macaques. Antisera (10–20 ml) were administered to macaques on day 8/9 of the luteal phase and serum samples collected during the treatment cycle and post-treatment cycle for determination of FSH, oestradiol and progesterone. In addition, localization of inhibin within the macaque ovary at this stage of the luteal phase was investigated using the ovine antiserum. Intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum with absence of staining in the thecalutein cells or other ovarian compartments. Administration of antisera was without significant effect on serum concentrations of FSH when compared with control animals, either during the first 24 h of detailed observation or for the following 10-day period of the late luteal phase and subsequent early follicular phase. These results provide further evidence that the corpus luteum is the major source of inhibin immunoreactivity during the primate menstrual cycle, but fail to support an endocrine role for inhibin in the suppression of FSH secretion.

Journal of Endocrinology (1992) 133, 341–347
The role of inhibin and oestradiol in the control of FSH secretion in the sheep
Authors: Mann G. E. , Campbell B. K. , McNeilly A. S. , Baird D. T.
Published: December 2008

The relative importance of inhibin and oestradiol in the control of FSH and LH secretion in the ewe was investigated by passive immunization in intact animals and by hormone replacement therapy following acute ovariectomy, in the same experiment. Mature Scottish Blackface ewes on day 10 of the luteal phase were allocated to nine groups of four to five animals. Four groups were ovariectomized and immediately treated with either progesterone alone or in combination with steroid-stripped ovine follicular fluid ('inhibin') and/or oestradiol. Three further groups of ewes were left intact and injected with antibodies to the 1–26α peptide fragment of porcine inhibin and/or oestradiol-17β. Two groups of animals were either ovariectomized alone with no further treatment, or were left intact and treated with normal sheep plasma to act as controls. Blood samples were collected at 2 h intervals from 12 h before until 48 h after ovariectomy/immunization, and from 12 to 24 h after treatment, blood samples were collected at 10-min intervals.

After ovariectomy there was a large rise in the peripheral concentration of LH (P < 0·001) which was not affected by treatment with progesterone alone but was completely prevented by treatment with progesterone and oestradiol. Treatment with inhibin had no effect on this post-castrational rise in LH. In intact ewes, immunization against oestradiol, alone or in combination with inhibin, resulted in a rise in the concentration of LH, while immunization against inhibin had no effect on LH concentration. The peripheral concentration of FSH showed a significant (P < 0·001) increase after ovariectomy which was not affected by treatment with progesterone alone. Treatment with inhibin or oestradiol alone caused a significant (P < 0·01) reduction in this rise, while treatment with inhibin and oestradiol together completely prevented this post-castrational rise in FSH concentration. Passive immunization against inhibin or oestradiol alone resulted in a transitory (P< 0·01) rise in the peripheral concentration of FSH, while immunization against the two hormones in combination resulted in a significantly (P < 0·01) larger rise. During the 14-h period after treatment, the rise in the concentration of FSH in this combined immunization group was not significantly different from that seen in the control ovariectomized group.

These results provide evidence that FSH secretion is under the control of both oestradiol and inhibin, while reinforcing the hypothesis that inhibin is not involved in the regulation of LH production, which is under the dual control of oestradiol and progesterone.

Journal of Endocrinology (1992) 133, 381–391
What is a normal stimulated growth hormone concentration?
Authors: Dattani M. T. , Pringle P. J. , Hindmarsh P. C. , Brook C. G. D.
Published: December 2008

In a retrospective analysis, we have compared the response of serum GH concentration to insulin-induced hypoglycaemia in 148 short prepubertal children (114 males, 34 females) aged between 3·9 and 11·9 years with the growth rate of the individual to determine 'cut-off' values for the diagnosis of GH insufficiency.

Sixty-three children grew with a height velocity standard deviation score (SDS) greater than −0·8 (group 1), which represents the growth velocity of children progressing along or closely parallel to the third height centile. Eighty-five children had a height velocity SDS of less than −0·8 (group 2). Median peak serum GH concentration responses to insulin-induced hypoglycaemia were 19·9 mU/l (range 1·5–54·4) in group 1 and 9·9 mU/l (range 0·7–46·2) in group 2 (Mann–Whitney; P < 0·001).

Using growth rate as the determinant of normality, the efficiency, sensitivity and specificity of the insulin-induced hypoglycaemia test were calculated using different serum GH concentration cut-off values to diagnose GH insufficiency. In our (Hybritech) assay, a cut-off value of 13·5 mU/l provided optimal performance in terms of efficiency (66%), sensitivity (64%) and specificity (70%).

The response of serum GH concentration to insulin-induced hypoglycaemia in short children growing at different growth rates was continuous. Each laboratory measuring serum GH concentrations needs to construct its own 'normal' cut-off value.

Journal of Endocrinology (1992) 133, 447–450
Glucocorticoid inhibition of stimulus-evoked adrenocorticotrophin release caused by suppression of intracellular calcium signals
Authors: Antoni F. A. , Hoyland J. , Woods M. D. , Mason W. T.
Published: December 2008

Stress provokes a cohort of homeostatic reflexes by the central nervous, the immune as well as the metabolic control systems of the body. These powerful adaptive responses, which can cause a collapse of body homeostasis in the absence of feedback inhibition, are suppressed by adrenal glucocorticoid hormones. A prominent and physiologically significant early action of glucocorticoids that requires the induction of newly synthesized messenger RNA and protein is the suppression of ACTH release by anterior pituitary corticotroph cells. It is demonstrated here that glucocorticoids inhibit stimulated ACTH secretion in pituitary corticotroph tumour (AtT-20) cells by reducing stimulus-evoked intracellular free calcium transients. Thus, the data show for the first time that intracellular calcium signals may be modified by rapidly induced proteins. It is proposed that this is a general mechanism that underlies the early inhibitory effects of glucocorticoids during stress in various types of cell.
Abnormal maternal behaviour in mice previously immunized against progesterone
Authors: Wang M.-W. , Heap R. B. , Taussig M. J.
Published: December 2008

Anti-progesterone immunization leads to reversible infertility in mice; this can be achieved by passive immunization with a monoclonal antibody to progesterone (DB3), or by active immunization with either a progesterone–protein (bovine serum albumin; BSA) conjugate or anti-idiotype directed against DB3. Recovery of fertility in treated females varied from 39·5 to 75·5 median days after passive or active (progesterone–BSA) immunization respectively. Litter size after the first pregnancy also differed from 8·6 ±0·8 to 5·0 ±0·6 (mean ± s.e.m.) per mother after passive or active immunization respectively. When litter size was standardized to a maximum of four pups per litter, aberrant maternal responses were observed in the first 5 days after delivery in 40–70% of the nursing mothers. These responses took the forms of cannibalism and failure to retrieve or to nurse pups and resulted in a high incidence of pup rejection (up to 40%), compared with no rejection in control mothers. When mothers were allowed to keep entire litters, an even higher incidence of pup rejection occurred (51% compared with 8% in controls). There was an apparent relation between the degree of negative maternal behaviour and the progesterone antibody concentration in the circulation during the infertile period. Whereas aberrant behaviour occurred mainly within the first 5 days of lactation, it was significantly reduced thereafter. Aberrant behaviour of the mother towards pups may be a consequence of the presence of residual progesterone antibodies in the circulation which affects the process of progesterone withdrawal at parturition that is essential for the establishment of normal maternal responses to the neonate.

Journal of Endocrinology (1992) 134, 257–267
Resistance to parathyroid hormone-induced inhibition of inorganic phosphate transport in opossum kidney cells cultured in low inorganic phosphate medium
Authors: Caverzasio J. , Bonjour J.-P.
Published: December 2008

Renal resistance to the phosphaturic action of parathyroid hormone (PTH) is observed during dietary deprivation of inorganic phosphate (Pi) in vivo. In the present work, the influence of short (3 h)- or long (72 h)-term deprivation of Pi on the effect of bovine PTH (bPTH(1–34)) on both Na-dependent Pi transport and cyclic AMP(cAMP) production was examined in cultured opossum kidney epithelium. Na-dependent Pi transport increased by 100% in cells exposed to low Pi medium containing no Pi (LPM) for 3 h, as compared with transport in high Pi medium containing 2 mmolPi/l (HPM). In response to a submaximal dose (1 nmol/l) of bPTH(1–34), Na-dependent Pi transport was similarly inhibited by about 40% in LPM and HPM. This inhibition was preceded by increased cAMP production which was identical in LPM and HPM. In opossum kidney cells exposed for 72 h to LPM, Na-dependent Pi transport was also increased by 100% compared with that in HPM. However, bPTH(1–34) added at 1 nmol/l did not induce any significant change in Na-dependent Pi transport or cAMP. Stimulation of cAMP could only be elicited at bPTH(1–34) concentrations higher than 1 nmol/l. Such a reduced cAMP response was also observed with forskolin in cells incubated for 72 h in LPM. The cellular resistance to the generation of cAMP was associated with a significantly lower level of ATP in cells cultured for 72 h in LPM compared with ATP levels in HPM. There was a good relationship between cellular ATP level and expression of the inhibitory effect of bPTH on Pi transport in culture media containing various concentrations of Pi. In conclusion, long-term Pi depletion in opossum kidney cells leads to cellular resistance to PTH-induced cAMP generation and inhibition of Pi transport. The lower level of cAMP in Pi-depleted cells is probably due to insufficient substrate for cAMP generation. It is likely that other ATP-dependent processes involved in cellular Pi transport regulation might also be affected in the severely Pi-depleted cells and contribute to the resistance of PTH action on Pi transport inhibition.

Journal of Endocrinology (1992) 134, 361–368