bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoplasmic and nuclear progesterone receptors in mouse mammary tumours during pregnancy determined by an improved hydroxylapatite assay
Authors: Koseki Y. , Costlow M. E. , Cole D. , Matsuzawa A. 
Published: December 2008

The binding of [3H] 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (R5020) to progesterone receptors in cytosol and nuclear extracts (0·6 m-KCl) of the pregnancy-dependent, TPDMT-4 mouse mammary tumour was measured at various stages of pregnancy. Compared with conventional dextran-coated charcoal (DCC) assays, a hydroxylapatite assay with DCC pretreatment and precharging of the cytosol with unlabelled R5020 (4 × 10−8 mol/l, for 3–4 h at 4 °C) showed the highest level of binding. The DCC treatment markedly increased the level of R5020 binding in both cytosol and nuclear extracts by allowing the receptor to bind to hydroxylapatite. The DCC pretreatment apparently removed a heat-stable and non-dialysable factor which prevented the receptor from binding to the hydroxylapatite. Using this assay R5020 binding reached a steady state in 24 h at 4 °C, with complete exchange of radioactive for non-radioactive ligand by 20 h. Nuclear extracts did not require precharging and complete exchange was more rapid. Scatchard analysis (without precharging) disclosed a single class of binding sites with a dissociation constant for cytosol of 3·2 ± 0·8 (s.e.m.) × 10−9 mol/l (n = 3) and 4·7 ± 0·6 × 10−9 mol/l (n = 5) for the nuclear extract. Binding was hormone-specific and progesterone translocated binding from the cytoplasm to the nucleus both in vivo and in vitro. Translocation, however, led to a substantial loss of total (nuclear + cytoplasmic receptors.
During pregnancy, cytoplasmic progesterone receptor levels were unchanged and low compared to nuclear progesterone receptors which increased by sevenfold from days 1 to 11 and then decreased at day 16. Compared with recent data on cytoplasmic progesterone receptors in normal mammary gland, our results suggested that this tumour may have a reduced sensitivity to the down-regulatory activity of progesterone. This lesion may, in part, account for the failure of the tumour to differentiate during pregnancy.
Goitrogen-induced thyroid growth in the rat: a quantitative morphometric study
Authors: Wynford-Thomas D. , Stringer B. M. J. , Williams E. D. 
Published: December 2008

This study was designed to investigate quantitatively the changes in thyroid morphology which accompany goitrogen-induced thyroid growth in the rat and to relate these changes to the level of serum thyrotrophin (TSH).
Animals treated with the goitrogen aminotriazole were killed, together with controls, at frequent intervals up to 153 days. A carefully controlled perfusion-fixation technique was employed, together with plastic embedding, to ensure optimal preservation of in-vivo morphology, and attention was paid to stereological principles in the methods of tissue sampling. Morphometric analysis was carried out by 'point-counting' to obtain the proportion of thyroid volume occupied by each of four components: epithelial cells, follicular lumen, blood vessels and non-vascular stroma. Total thyroid weight was measured, from which the total volumes of each component were calculated. Serum TSH was measured by radioimmunoassay.
Goitrogen treatment led to a rapid rise in the level of serum TSH, reaching a sustained fivefold maximum by day 82. Total thyroid weight increased to a 12-fold plateau after 116 days. There was a rapid change during the first week in the proportional volumes of component tissues; a rise in the epithelial cell and blood vessel components being accompanied by a corresponding fall in follicular lumen and non-vascular stroma. Total epithelial cell volume rose in parallel with thyroid weight to reach a 16-fold maximum. There was a more marked (34-fold) increase in vascular volume and there were smaller increases in the other two components. No significant growth occurred after 116 days.
The results show that goitrogen-induced changes in thyroid morphology are complete at submaximal levels of TSH stimulation and that growth then proceeds by a proportional increase in all components. The morphological changes persist, but growth eventually ceases, despite a sustained rise in the level of serum TSH, thus pointing to the existence in the thyroid of a growth-limiting control mechanism.
Plasma concentrations and urinary excretion of mouse epidermal growth factor associated with the inhibition of food consumption and of wool growth in Merino wethers
Authors: Panaretto B. A. , Moore G. P. M. , Robertson D. M. 
Published: December 2008

Twenty-four adult Merino wethers were given mouse epidermal growth factor (mEGF) subcutaneously at doses ranging from 0·02 to 0·12 mg/kg body weight or intravenously in the dose range 010 to 0·14 mg/kg body weight for periods ranging from 3 to 48 h. Plasma concentrations of mEGF were measured by radioimmunoassay and effects of treatment on food consumption and wool growth were observed.
Plasma concentrations of the protein sustained for 15–24 h at about 20 ng mEGF/ml (or exceeding this) almost invariably caused feed rejection and casting of the fleeces. This last result clearly indicated disruption of proliferative activity among the replicating cells in wool follicles which regulate wool growth.
The inhibitory effects on appetite and wool growth of smaller doses of the protein and of plasma concentrations equal to those above which were sustained for shorter periods have also been examined.
Approximately 10% of the dose of mEGF appeared in the urine of three sheep 1 to 3 days after the start of s.c. infusions of 5 mg for 7 h.
Prolactin secretion and dopamine receptors of the MtTW15 transplantable pituitary tumour
Authors: Cronin M. J. , Keefer D. A. , Valdenegro C. A. , Dabney L. G. , MacLeod R. M. 
Published: December 2008

The MtTW15 transplantable pituitary tumour grown in rats was tested in vitro for the ability of dopamine agonists to affect prolactin secretion and for the existence of dopamine receptors. Prolactin release from enzymatically dispersed cells and non-enzymatically treated tissue fragments of both the tumour and the anterior pituitary gland was determined in a cell perifusion column apparatus. Dopamine (0·1–5 μmol/l), bromocriptine (50 nmol/l) and the dopamine antagonist haloperidol (100 nmol/l) had no effect on prolactin release from the tumour cells. In contrast, dopamine (500 nmol/l) inhibited prolactin secretion from normal anterior pituitary cells in a parallel cell column and haloperidol blocked this inhibition. Although oestrogen treatment in vivo stimulated prolactin release in vitro when the tumour was removed and studied in the cell column, oestrogen had no effect on the inability of dopamine to modify the prolactin secretion. Growth hormone release from the tumour cells was not affected by dopamine.
Although MtTW15 cells were refractory to dopaminergic inhibition of prolactin release, the dopamine receptors present in tumour homogenates were indistinguishable from the dopamine receptors previously defined in the normal anterior pituitary gland. The binding of the dopamine antagonist [3H]spiperone to the tumour was saturable (110 fmol/mg protein), of high affinity to one apparent class of sites (dissociation constant = 0·12 nmol/l), reversible and sensitive to guanine nucleotides. The pharmacology of the binding was defined in competition studies with a large number of agonists and antagonists. From the order of potency of these agents, a dopaminergic interaction was apparent. We conclude that the prolactin-secreting MtTW15 tumour cells appear to be completely unresponsive to dopamine or to the potent dopamine agonist bromocriptine, in spite of apparently normal dopamine receptors in the tumour.
The origin of cortisol in the blood of fetal sheep
Authors: Hennessy D. P. , Coghlan J. P. , Hardy K. J. , Scoggins B. A. , Wintour E. M. 
Published: December 2008

The blood clearance rate (BCR) of cortisol was measured in non-pregnant ewes and in pregnant ewes and their intact or bilaterally adrenalectomized fetuses. In pregnant sheep the placental transfer of cortisol in both directions was established. The BCR of cortisol in the non-pregnant sheep was 51·7±4·9 (s.e.m.)1/h (n = 36) or 1·151/h per kg body weight. This was lower than that in the pregnant ewe (97–143 days of gestation) of 76·9±4·21/h (n = 9) or 1·851/h per kg.
In the intact fetus the BCR was 8·2±0·261/h (n = 10) over the same period of gestation. The percentage of the maternal production rate of cortisol transferred to the fetus was 1·4±0·11% (n = 9) and the placental transfer from fetus to mother was 19·5±1·5% (n = 8). The BCR in pregnant ewes bearing bilaterally adrenalectomized fetuses was not significantly different from that of mothers of intact fetuses (58·4±7·71/h; n = 6). The BCR of adrenalectomized fetuses was 8·4±1·371/h (n = 8). The placental transfer of cortisol from mother to fetus was sufficient to account for all the cortisol measured in adrenalectomized fetuses and in intact fetuses of 100–121 days of gestation. However, it accounted for only 37% of the cortisol measured in fetuses of 122–135 days of gestation and 12% or less in fetuses older than 136 days of gestation.
Direct effect of melatonin on the accessory sexual organs in pinealectomized male rats kept in constant darkness
Authors: Shirama Kazuhiko , Furuya Tetsuo , Takeo Yuji , Shimizu Kiyoshi , Maekawa Kyutaro 
Published: December 2008

Pinealectomized and sham-pinealectomized male rats were subcutaneously implanted with 2 cm silicone elastomer capsules filled with testosterone or dihydrotestosterone (DHT) and placed in constant darkness (DD) for 50 days. The data revealed that the sham-pinealectomized group treated with testosterone differed from the pinealectomized group, having lower weights of accessory sexual organs and levator ani muscle. Pinealectomy had no effect on organ and muscle weights of DHT-treated animals.
Exposure of male rats to DD resulted in a marked decrease in weights of ventral prostate, seminal vesicle, coagulating gland and levator ani muscle and a decrease in plasma DHT levels. However there was no significant reduction in plasma LH, FSH or testosterone. Pinealectomy of the rats exposed to DD resulted in restoration of both DHT levels and accessory sex organ weights. Melatonin implants in pinealectomized males led to an increase in both testosterone and DHT levels, accompanied by a decrease in sexual organ weights. The data indicate that the anti-gonadal effect of the pineal gland cannot be completely mediated by melatonin and that melatonin and some unknown factors can act at the tissue level to reduce the size and function of the affected sexual organs.
Effect of corticosterone on the hypothalamic-pituitary-gonadal system of male Japanese quail exposed to either short or long photoperiods
Authors: Deviche Pierre , Massa Renato , Bottoni Luciana , Hendrick Jean-Claude 
Published: December 2008

Male quail were bred under short photoperiods of 8 h light: 16 h darkness (8L : 16D; SD) for the first 4 weeks of life and were then transferred to either long photoperiods of 16L : 8D (LD) or maintained under the SD regime. Both groups of birds were treated for 2 weeks with a daily dose of either 0·25 or 1·0 mg corticosterone. The conversion of [14C]testosterone in vitro into 5α- and 5β-dihydrotestosterone (5α- and 5β-DHT), 5α- and 5β-androstane-3α,17β-diol, and androstenedione was then measured in the pituitary and cloacal glands of all birds. In the hyperstriatum and posterior hypothalamus only 5β-reduced metabolites and androstenedione were detected.
Transfer to LD and injection of corticosterone affected the metabolism of testosterone only in the pituitary and cloacal glands. In the pituitary gland, exposure to LD increased the production of 5α-reduced metabolites but not of either 5β-reduced metabolites or androstenedione. In both SD and LD birds, injections of corticosterone enhanced the production of 5β-reduced steroids and decreased the production of androstenedione. In LD birds corticosterone also decreased the production of 5α-androstane-3α,17β-diol. Plasma levels of LH and FSH were higher in the LD than in the SD birds. In the SD birds treatment with corticosterone increased the level of LH after 14 days of treatment. Exposure to LD decreased the production of 5β-androstane-3α,17β-diol and androstenedione in the cloacal gland and increased the conversion of testosterone into 5α-DHT Treatment with corticosterone increased the production of androstenedione in the cloacal gland of LD birds but decreased it in that of SD birds. Corticosterone also partially blocked the photoinduced growth of the cloacal gland, but it slightly stimulated the growth of the gland in the SD birds. After 2 weeks of treatment SD (but not LD) corticosterone-treated birds had higher testicular weights than the corresponding controls.
It is suggested that treatment with corticosterone might affect the hypothalamic-pituitary-gonadal axis partly through changes in the metabolism of testosterone.
Preparation and steroidogenic properties of purified zona fasciculata and zona reticularis cells from the guinea-pig adrenal gland
Authors: Hyatt P. J. , Bell J. B. G. , Bhatt K. , Tait J. F. 
Published: December 2008

Mixtures of zona fasciculata (ZF) and zona reticularis (ZR) cells, obtained by enzyme dispersion of decapsulated guinea-pig adrenal glands, were separated either by unit gravity sedimentation or by equilibrium density sedimentation. There was no evidence of deleterious effects on ultrastructural integrity or the ability of cells to respond to (1–24)ACTH (Synacthen) after either separation technique. Unit gravity sedimentation gave one fraction in which 90% of the cells were from the ZR and another fraction in which 70% of the cells were from the ZF. Equilibrium density sedimentation of cell mixtures on Percoll gradients gave fractions containing either 90% pure ZR or 95% pure ZF cells.
Cortisol, 11-deoxycortisol, corticosterone, deoxycorticosterone, 11 β-hydroxyandrostenedione and androstenedione were all formed from [14C]pregnenolone on incubation with purified preparations of both types of cell. No product was seen to be unique to either cell type although ZR cells appeared deficient in 11β-hydroxylase activity relative to ZF cells. The ratio of androstenedione to cortisol (formed either from labelled pregnenolone or from endogenous precursors) was higher for ZR cells than for ZF cells. When the purer cells obtained by equilibrium density sedimentation were studied, it was found that (1–24)ACTH stimulated greater steroid production (both androstenedione and cortisol) by the ZF cells compared with the ZR cells.
Effect of porcine follicular fluid preparations on gonadotrophin secretion by the mouse pituitary gland in vitro
Authors: Kato K. , Sairam M. R. , Ramasharma K. 
Published: December 2008

The acute effects of pooled porcine follicular fluid (PFF), before and after various methods of processing to eliminate steroids, were studied on the luteinizing hormone releasing hormone (LH-RH)-induced release of FSH and LH by whole pituitary glands, from 34-day-old mice, incubated in vitro for 3–4 h. Charcoal treatment of PFF eliminated the steroids and reduced the inhibitory potency on gonadotrophin secretion. On the other hand, dialysis or ultrafiltration (mol. wt > 10 000) did not reduce the inhibitory activity on gonadotrophin secretion.
Of the three steroids tested, only oestradiol at a concentration of 10−10 mol/l inhibited FSH and LH secretion in vitro. This inhibitory effect was counteracted by the inclusion of the oestrogen antagonist tamoxifen in the incubation medium. The presence of tamoxifen did not decrease the suppression of FSH and LH induced by PFF, suggesting that the inhibition observed under the conditions of incubation was not due to oestrogen. Preincubation of mouse pituitary tissue for 1 h with PFF reduced the subsequent release of bioactive FSH and LH induced by LH-RH. The inhibitory effect of PFF was rapid and sustained. The continuous presence of PFF throughout the incubation period was not necessary for manifestations of the inhibitory effects on gonadotrophin release. The suppression of gonadotrophin secretion was related to the dose of PFF with the curve showing a biphasic pattern. The degree of FSH suppression was uniformly greater than that of LH, showing the preferential nature of the inhibitory effect of PFF. At high doses of PFF, the degree of FSH suppression was decreased significantly. This effect on LH release was less pronounced.
The inhibition caused by PFF in the in-vitro incubation procedure was not due to destruction of LH-RH or the released gonadotrophins.
Time-course of release and synthesis of luteinizing hormone, follicle-stimulating hormone and prolactin from rat pituitary glands in vitro
Authors: Apfelbaum Marta E. 
Published: December 2008

To study the time-course of release and synthesis of LH, FSH and prolactin, anterior pituitary glands from ovariectomized rats were incubated for different time-intervals between 0 and 4 h.
Comparable patterns of release and synthesis of LH and FSH as a function of the incubation time were observed. It was possible to distinguish two phases in the profiles of secretion of both gonadotrophins. During the first phase, from 0–2 h, release was associated with a corresponding decrease of the hormone concentrations within the gland but no overall changes in total LH and FSH production. During the second phase, between 2 and 4 h, a progressive reaccumulation of both gonadotrophins occurred in spite of the continuous release of hormones into the medium, reflecting formation of new immunoassayable material. These results suggest that the increased synthesis ensues as a secondary phenomenon arising from the release of the hormones from the tissue. The time-course of release and synthesis of prolactin showed different dynamics during the course of incubation. High levels of prolactin were released and synthesized when the adenohypophysis was incubated in vitro. Considerably larger amounts of this hormone were found in the medium than in the tissue from the first hour of incubation. After a lag of about 40 min synthesis of prolactin was increased in parallel with its release. This led to the assumption that both prolactin synthesizing and releasing processes occurred simultaneously from the early stages of the incubation. Comparatively, prolactin-secreting cells had a very fast and LH-secreting cells a low rate of turnover; FSH-secreting cells were intermediate between the two.
These results indicate that (1) the increase in release of LH, FSH and prolactin into the medium precedes that of hormone synthesis and (2) the initial depletion of the pituitary gland as a result of hormone release could act as a stimulus for synthesis, leading to the reestablishment of hormonal storage levels.
The corticotrophic cells of the canine pituitary gland in pituitary-dependent hyperadrenocorticism
Authors: McNicol A. M. , Thomson H. , Stewart C. J. R. 
Published: December 2008

The distribution of specifically stained corticotrophic cells has been studied in the pituitary glands of 11 dogs with pituitary-dependent hyperadrenocorticism. The results suggest that the disease is not a single entity, and that some cases are caused by primary abnormality of the pituitary gland whereas others appear to be the result of dysfunction of the hypothalamus or central nervous system.
The patterns correspond closely to those demonstrated in the human pituitary gland in Cushing's disease, and confirm that the canine disease is a useful model for the study of the pathogenesis of the variants of the condition.
Influence of streptozotocin-induced diabetes in pregnant rats on plasma corticosterone and progesterone levels and on cytoplasmic glucocorticoid receptors in fetal tissues
Authors: Mulay S. , Solomon S. 
Published: December 2008

Administration of a dose of 45 mg streptozotocin/kg on day 2 of gestation produced a diabetic state in pregnant rats and was associated with fetal hyperinsulinaemia. Although there was no evidence of fetal macrosomia, the ratio of fetal liver and lung weight to body weight was greater in fetuses of diabetic rats, suggesting an increase in the size of these organs relative to the body weight.
Maternal and fetal plasma corticosterone levels of diabetic rats between 19 and 22 days of gestation was significantly lower than the corresponding control values. Maternal plasma progesterone levels of diabetic rats were lower than controls on days 19 and 20 of gestation, but higher than controls on day 21 of gestation. The absence of pregnancy-related changes in maternal and fetal plasma corticosterone levels and maternal progesterone levels in diabetic rats suggest that adrenocortical function as well as ovarian and/or placental function may be impaired, which may in turn be related to the observed delay in parturition of approximately 18 h as well as to the low survival rate of the pups.
There was a small increase in the cytoplasmic glucocorticoid receptor concentration in the lung but not in the liver of fetuses of diabetic mothers when compared with fetuses of controls, suggesting that the increased receptor concentration may be a compensatory mechanism to overcome the effect of decreased corticosterone levels and increased insulin levels in the fetuses of diabetic rats.
Plasminogen activator in rat ovary during the ovulatory process: independence of prostaglandin mediation
Authors: Shimada Hayato , Okamura Hitoshi , Noda Yōichi , Suzuki Akira , Tōjō Shimpei , Takada Akikazu 
Published: December 2008

To elucidate the possible roles of increased plasminogen activator (PA) in follicular rupture and to investigate whether prostaglandins participate in ovarian PA synthesis in vivo, enzyme activities were sequentially measured by a method using the chromogenic substrate S-2251 in immature rat ovaries primed with pregnant mare serum gonadotrophin (PMSG) followed by human chorionic gonadotrophin (hCG) either alone or with a concurrent injection of indomethacin.
Before hCG injection PA activity was 0·006 ± 0·006 (s.d.) μmol/1·6 mg ovarian tissue (wet wt) per 30 min: PA activity of a saline-treated group remained at low levels (<0·018 ± 0·003 μmol/1·6 mg tissue per 30 min). In contrast, PA activity of animals given hCG alone increased after the treatment, reaching a peak value of 0·112 ± 0·071 μmol/1·6 mg tissue per 30 min 12 h later, before decreasing to 0·023 ± 0·014 μmol/1·6 mg tissue per 30 min at 32 h. Contrary to expectations, a dose of indomethacin which completely blocked ovulation had no effect on either the magnitude or the time-course of PA synthesis after hCG administration (P>0·05).
These results indicate that prostaglandins are not involved in the preovulatory synthesis of PA induced by hCG in rat ovaries and that PA is not a primary proteolytic enzyme for follicular rupture. It is suggested that PA has possible roles in cumulus detachment and/or proliferation of granulosa cells during the ovulatory process.
Incidence of ovulation in the years after the menarche
Authors: Metcalf M. G. , Skidmore D. S. , Lowry G. F. , Mackenzie J. A. 
Published: December 2008

Urine for the analysis of pregnanediol was collected weekly for 3 months from 209 menstruant women aged 11–24 years who lived with their parents and from 59 women aged 17–23 years who had left the parental home. Menstrual cycles were classed as ovulatory if the 24-h pregnanediol output in the 12 days preceding menstruation was ≥ 5 μmol on a single occasion or if the total excreted on 2 days, 1 week apart, was ≥ 7 μmol.
In the first group, ovulatory incidence increased with menarchal age. Unfailing ovulation occurred in 22·9, 25·0,44·8,42·9, 63·2, 71·8 and 82·6% of those who were < 1, 1−<2, 2−<3, 3−<4, 4−< 5, 5–8 and 9–12 years from menarche. Comparable figures for the women who lived in flats and hostels were 40·0% (menarchal age, 5–8 years) and 78·6% (9–12 years).
It is concluded that a regular pattern of ovulatory menstrual cycles is established in most young women within 5 years of the menarche, and that departure from the family home is often associated with a regression to a juvenile pattern of anovulatory menstrual cycles.