Search Results
You are looking at 1 - 10 of 13 items for
- Author: M. WELLS x
- Refine by access: All content x
Search for other papers by M. WELLS in
Google Scholar
PubMed
The routine procedure in this laboratory for the extraction of gonadotrophins from urine is a kaolin-acetone method (Brown, 1959). Recently, we have started using a new bioassay depending on induced ovulation in mice (Cunningham, 1962). The present investigation was undertaken to discover whether any other extraction methods would give consistently higher yields than Brown's method when gonadotrophin was measured by the ovulation assay. The methods selected are shown in Table 1. They were chosen as being comparable in speed and convenience with the method in present use; more laborious techniques such as those employing ethanol precipitation were excluded since they are unsuitable for routine use.
Techniques of extraction and grades of reagents were all similar to those specified in the published descriptions. Where the specified quantities were given in relation to a 24 hr. specimen, this was taken as equivalent to 1200–1500 ml. urine. The dried extracts were stored at
Search for other papers by T. Wells in
Google Scholar
PubMed
Search for other papers by M. L. Forsling in
Google Scholar
PubMed
ABSTRACT
A series of studies has been performed in the conscious rat to investigate the effect of the intracerebroventricular (i.c.v.) administration of the selective κ-opioid receptor agonist, U50 488H, on arginine vasopressin (AVP) secretion stimulated by i.c.v. administration of hypertonic NaCl. Similarly, the effect of the i.c.v. administration of morphine and the i.v. administration of naloxone on AVP secretion was investigated. The response of AVP to an i.c.v. injection of hypertonic NaCl was potentiated by naloxone at a dose of 0·4 mg/kg, but a higher dose (1·2 mg/kg) was required to increase the basal plasma concentration of AVP. Prior treatment with U50 488H or morphine attenuated the increase in plasma concentrations of AVP stimulated by i.c.v. injection of hypertonic NaCl from 13·92±4·44 to 1·22±0·34 and 1·78±0·74 pmol/l respectively (n = 7; P<0·05). Prior administration of U50 488H also attenuated the potentiating effect of naloxone on AVP secretion stimulated by i.c.v. injection of hypertonic NaCl. These results indicate that basal AVP secretion is under tonic inhibitory control by dynorphin, and that μ-and κ-opioid receptors mediate an inhibitory influence of endogenous opioids on osmoreceptor-mediated AVP secretion.
Journal of Endocrinology (1991) 129, 411–416
Search for other papers by P. S. BROWN in
Google Scholar
PubMed
Search for other papers by M. WELLS in
Google Scholar
PubMed
SUMMARY
The response to gonadotrophins in an assay based on the induction of ovulation in immature mice was reduced by treatment of the experimental animals with barbitone. The responses to follicle-stimulating hormone and luteinizing hormone (LH) were reduced to a similar degree. Lack of specificity of the assay for LH is probably not due simply to the endogenous secretion of this hormone.
Progesterone and oestradiol-17β had no definite effect on the assay but norethynodrel significantly reduced the slope of the dose-response line. Feeding the mice with methylthiouracil increased the sensitivity to a small but significant extent.
Assays depending on the induction of ovulation in immature, pregnant and mature dioestrous mice were compared. Mice of the first two types gave more sensitive and precise assays of human urinary gonadotrophin.
Search for other papers by P. S. BROWN in
Google Scholar
PubMed
Search for other papers by M. WELLS in
Google Scholar
PubMed
SUMMARY
The follicle-stimulating hormone (FSH) content of urinary gonadotrophic extracts was assayed by its effect on the ovarian weight of immature mice when given in conjunction with 40 i.u. human chorionic gonadotrophin. About three-quarters of all routine assays gave values of λ between 0·15 and 0·30. Precision was slightly increased when the material was given in three rather than in five injections. Correction of ovarian weight for body weight was either invalid or of no value in reducing variance. Removal of between-litter variance increased precision considerably. Mice of three randomly bred colonies were all satisfactory, and inbred C57BL mice were also suitable for the assay. C3H mice were less sensitive.
The efficiency of different methods of extracting FSH from urine was examined. The method of Johnsen (1958) using precipitation with tannic acid was considered the most satisfactory and gave extracts of high potency and low bulk.
Limited experiments in which purified human pituitary FSH was assayed with and without added luteinizing hormone, gave results compatible with the assumption that the method is specific for FSH.
Search for other papers by M. WELLS in
Google Scholar
PubMed
Search for other papers by T. KHOSLA in
Google Scholar
PubMed
Search for other papers by P. S. BROWN in
Google Scholar
PubMed
SUMMARY
An assay method depending on the induction of ovulation in immature mice has been applied to the assay of human urinary gonadotrophin, human chorionic gonadotrophin, pregnant mare serum gonadotrophin, and sheep and rat pituitary gonadotrophins. Valid parallel line assays were obtained in all cases, and the sensitivity and precision of the assay were such as to make it suitable for application to clinical studies.
Experiments with mixtures of gonadotrophins, and the use of a barbiturate to suppress gonadotrophin secretion, indicate that the assay was not specific for LH. It is suggested that the lack of specificity may be due in part to the secretion of a variable amount of gonadotrophin by the pituitaries of the test animals.
Search for other papers by RALPH HARSH in
Google Scholar
PubMed
Search for other papers by M. D. OVERHOLSER in
Google Scholar
PubMed
Search for other papers by L. J. WELLS in
Google Scholar
PubMed
Our purposes in this study were to ascertain the effects of oestrogen on the accessory reproductive organs of male mice and rats, and to determine the capacity of androgen to counteract these effects.
Methods
The oestrogen, Amniotin, was furnished by Dr. J. A. Morrell of E. R. Squibb and Sons; and the androgen, testosterone, was supplied by Dr. Erwin Schwenk of the Schering Corporation.
Seventy-two rats and 71 mice have been used in this study. Thirty-one rats were given injections of oestrogen. The other 41 rats, litter-mates to the treated animals, received no injections. In the case of mice, 36 received only oestrogen, 13 were given oestrogen and testosterone, and 22 controls received no injections. The control mice in most cases were not litter-mates of injected animals.
Both testes were surgically removed from some of the animals. The immature rats were castrated on the 17th–24th day of life. The adult
Search for other papers by M. BEN-DAVID in
Google Scholar
PubMed
Search for other papers by A. DANON in
Google Scholar
PubMed
Search for other papers by R. BENVENISTE in
Google Scholar
PubMed
Search for other papers by C. P. WELLER in
Google Scholar
PubMed
Search for other papers by F. G. SULMAN in
Google Scholar
PubMed
SUMMARY
Treatment for 5 days of female rats with perphenazine (5 mg/kg/day) induced full lobulo—alveolar differentiation. Long-standing adrenalectomy (12 days) decreased this mammotrophic effect of perphenazine. The mechanism of this reaction was studied in male rats in order to avoid fluctuations of the prolactin content in the anterior pituitary. Adult male rats were adrenalectomized and injected s.c. after 12 days with perphenazine (10 mg/kg). Two hours later the rats were killed and pituitary and serum prolactin levels assayed by double antibody radioimmunoassay. In intact rats, perphenazine treatment enhanced serum prolactin up to 104 ± 4 (s.e.m.) ng/ml (± 350%). Adrenalectomy alone increased serum prolactin from 30± 5 to 47 ± 6 ng/ml (+56%), and augmented the perphenazine-induced release of prolactin from the pituitary into the blood from 104 ± 4 to 147 ± 10 ng/ml (+ 42%).
In chronically adrenalectomized adult female rats extremely high amounts of prolactin (+ 1617%) were detected in the serum at the end of 5 days' treatment with perphenazine (5 mg/kg/day).
These results indicate that removal of the adrenals in male and female rats does not interfere with the ability of the pituitary to secrete prolactin. Moreover, they also show that in adrenalectomized rats the impaired mammotrophic effect of perphenazine is not due to prolactin deficiency (since high serum levels of this hormone were present) but to the absence of corticosteroids at the target organ.
Search for other papers by Timothy J Dreyer in
Google Scholar
PubMed
Search for other papers by Jacob AC Keen in
Google Scholar
PubMed
Search for other papers by Leah M Wells in
Google Scholar
PubMed
Search for other papers by Scott J Roberts in
Google Scholar
PubMed
As a key regulator of bone homeostasis, sclerostin has garnered a lot of interest over the last two decades. Although sclerostin is primarily expressed by osteocytes and is well known for its role in bone formation and remodelling, it is also expressed by a number of other cells and potentially plays a role in other organs. Herein, we aim to bring together recent sclerostin research and discuss the effect of sclerostin on bone, cartilage, muscle, liver, kidney and the cardiovascular and immune systems. Particular focus is placed on its role in diseases, such as osteoporosis and myeloma bone disease, and the novel development of sclerostin as a therapeutic target. Anti-sclerostin antibodies have recently been approved for the treatment of osteoporosis. However, a cardiovascular signal was observed, prompting extensive research into the role of sclerostin in vascular and bone tissue crosstalk. The study of sclerostin expression in chronic kidney disease was followed by the investigation of its role in liver–lipid–bone interactions, and the recent discovery of sclerostin as a myokine prompted new research into sclerostin within the bone–muscle relationship. Potentially, the effects of sclerostin reach beyond that of bone alone. We further summarise recent developments in the use of sclerostin as a potential therapeutic for osteoarthritis, osteosarcoma and sclerosteosis. Overall, these new treatments and discoveries illustrate progress within the field, however, also highlight remaining gaps in our knowledge.
Search for other papers by J M Brameld in
Google Scholar
PubMed
Search for other papers by P A Weller in
Google Scholar
PubMed
Search for other papers by J C Saunders in
Google Scholar
PubMed
Search for other papers by P J Buttery in
Google Scholar
PubMed
Search for other papers by R S Gilmour in
Google Scholar
PubMed
Abstract
The effects of various hormones commonly added to hepatocyte culture media upon the expression of the GH receptor (GHR) and insulin-like growth factor-I (IGF-I) genes in cultured porcine hepatocytes were investigated. Preliminary investigations indicated that there was an absolute requirement only for insulin, with high losses of cell viability upon long term exclusion of insulin from the culture medium. The decline in GHR expression with time in culture was found to be less when high levels of glucose were included in the medium. Therefore the basal culture medium used in these studies was Williams' medium E supplemented with 0·2% (w/v) BSA, 5000 mg glucose/l and 100 nmol porcine insulin/l. The addition of dexamethasone (100 nmol/l) increased the expression of both GHR and IGF-I (class 1 transcripts only) mRNA (P<0·001 and P<0·05 respectively), and resulted in an increased responsiveness of IGF-I mRNA expression to GH (1 μg/ml), when the two were added in combination (although only class 1 transcripts were shown to be statistically significant, P<0·01). The addition of either thyroid hormone (1 nmol/l T3 or T4) alone also increased the expression of GHR mRNA (P<0·01) in addition to the dexamethasone stimulated expression, with T4 appearing to decrease IGF-I expression slightly (P<0·05) (either on its own or with T3). As with dexamethasone, the thyroid hormones increased the response of IGF-I mRNA expression to GH (1 μg/ml) when added in combination with GH (P<0·001). These observations demonstrate one possible mechanism for the interactions of glucocorticoids and thyroid hormones with the GH–IGF axis.
Journal of Endocrinology (1995) 146, 239–245
Search for other papers by P. J. Coates in
Google Scholar
PubMed
Search for other papers by I. Doniach in
Google Scholar
PubMed
Search for other papers by C. Wells in
Google Scholar
PubMed
Search for other papers by A. C. Hale in
Google Scholar
PubMed
Search for other papers by L. H. Rees in
Google Scholar
PubMed
Search for other papers by G. M. Besser in
Google Scholar
PubMed
ABSTRACT
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