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Biomedical subjects

R W Shaw

Publications and source records attributed to R W Shaw.

At least 217 records · Page 12Linked to original sources
PubMed1976

Hydrogen ion titration of horse heart ferricytochrome c.

Continuous hydrogen ion titration curves of deionized solutions of horse heart ferricytochrome c have been obtained at 25 degrees C. at a constant ionic strength of 0.10 from pH 3.0 to 11.0. Titration of the oxidized protein in KCl required 28.4 equiv over that pH range, and a small hysteresis between the forward and reverse limbs was displayed. The Linderstrom-Lang approximation, which takes into account electrostatic interactions between charged groups on the protein surface, was used in a computer simulation program to analyze the forward and reverse limbs of the titration curve separately. The results indicated 1 alpha-, 12 beta- and gamma-, and 1 heme propionic carboxylic, 1 imidazole, 1 phenolic, and 18 epsilon-amino residues appear to titrate normally. Variations in the electrostatic interaction factor omega suggest conformational changes in the protein at the extremes of pH, although the relationship of the variations in omega to the magnitude of the conformational changes does not appear to be strictly quantitative for cytochrome c. These results show the acid-base behavior of cytochrome c to be complex in nature, and suggest that the Lindenstrom-Lang model may not be adequate for cytochrome c.

Animals↗
PubMed1976

Modification by sex steroids of LHRH response in the polycystic ovary syndrome.

Exogenously administered oestradiol or progesterone was found to induce augmentation of LH and FSH release in response to LHRH administration in patients with the polycystic ovary (PCO) syndrome. The effect of oestradiol upon LH release in the patients was significantly less than the augmented release induced in normal women (P less than 0-02). In contrast, progesterone induced a significantly greater LH release in PCO patients than normal women studied during the early follicular phase (P less than 0-001) but less than that in normal women studied during the mid-follicular phase of the cycle (P less than 0-01). The effects on FSH release in the PCO patients were less marked but similar to those in normal women with comparable basal steroid levels. The results suggest that both oestradiol and progesterone can modify the hypothalamic-pituitary axis in the PCO syndrome in a manner similar to that observed in normal women and a failure of these 'positive feedback' mechanisms does not appear to be the cause of the ovulatory deficiency in this syndrome.

Clinical Trials as Topic↗
PubMed1976

The control of gonadotrophin release in women with hyperprolactinaemic amenorrhoea: effect of oestrogen and progesterone on the LH and FSH response to LHRH.

The effect of the administration of oestradiol benzoate and of progesterone on the subsequent response to LHRH has been investigated in women with hyperprolactinaemia. There was an amplification in the release of LH in four out of ten patients and of FSH in one out of ten patients at 44 h after the administration of 2-5 mg oestradiol benzoate. The average amount of LH released before and after oestrogen did not change, but there was a significant decrease in the amount of FSH released. There was no correlation between the LH released and the oestradiol concentration in serum at the time of the LHRH tests but there was a negative correlation between the FSH released and the oestradiol concentration (r = 0-507;P less than 0-05). These results contrast with those obtained in normal subjects in the follicular phase of the cycle when there is a positive correlation of oestrogen concentrations and the amount of LH and FSH released. As in normal subjects, however, a significant suppression of basal FSH concentrations, persisting until 44 h, was produced by the oestrogen (P less than 0-01). Seven out of eleven patients showed an amplification of LH response and six out of eleven an FSH response 20 h after the administration of 25 mg progesterone. The mean amplifications are not significantly different from those of normal subjects tested in the early follicular phase of the cycle, but are significantly less than those tested in the mid follicular phase of the cycle (LH P less than 0-001; FSH P less than 0-01). This may be related to the serum concentrations of oestradiol which in patients with hyperprolactinaemia are significantly less than those found in the mid follicular phase of the cycle (P less than 0-05). These results indicate that in women with hyperprolactinaemia oestrogen negative feedback, necessary for cycle initiation, is normal: failure of ovulation may be related to failure of positive feedback to oestroen. Oestrogen-negative feedback is unopposed and this may explain the follicullar development and lack of oestrogen in the mid-follicular phase.

Amenorrhea↗
PubMed1976

Tests of the hypothalamic-pituitary-ovarian axis.

The availability of RIA to measure the pituitary gonadotropins and ovarian sex steroids has greatly helped in the development of tests of hypothalamic-pituitary-ovarian function. The use of estimates of basal gonadotrophin and sex steroid hormones together with dynamic tests such as the LH-RH test, oestrogen provocation test, clomiphene tests and exogenous gonadotrophins can now test the integrity and functional capacity of each of the components of the HPO axis. Figure 4 demonstrates how these tests can be used in a logical sequence to investigate patients with a disorder of the HPO axis after having first excluded any other endocrine abnormality. Screening of serum for elevated levels of gonadotrophins, prolactin and progesterone is an important initial step. Interpretation of the oestrogen provocation and clomiphene tests requires a normally functioning pituitary gland and hence the response to an LH-RH test also plays a ket role. The flow chart also demonstrates the points at which specific ovulation induction treatment can be instituted and should be useful in saving patient and doctor investigative time. Using these types of tests it should be possible to reclassify disorders of the HPO axis on the basis of their underlying pathology.

Androgens↗
PubMed1975

An abnormality of oestrogen feedback in amenorrhoea-galactorrhoea.

Fourteen patients with amenorrhoea and hyperprolactin-anemia but no evidence of pituitary tumours were each given an intramuscular injection of 1 mg oestradiol benzoate. Thirteen patients failed to release luteinizing hormone in response to the oestrogen. This hypothalamic abnormality may help to explain the menstrual disturbances in subjects with hyperprolactinaemia.

Amenorrhea↗
PubMed1975

The oestrogen provocation test: a method of assessing the hypothalamic-pituitary axis in patients with amenorrhoea.

The oestrogen feedback and gonadotrophin release in ten amenorrhoeic women were investigated, using intramuscular injection of 1 mg oestradiol benzoate. Serial estimations of serum oestradiol and gonadotrophins (LH and FSH) were made over a period of 72 h following the injection. Five patients demonstrated positive feedback release of LH to the oestrogen stimulus with elevated levels of LH significantly above baseline (P less than 0.001), which occurred between 48 and 72 h after the injection. Two of the five patients also demonstrated elevated FSH levels accompanying these LH peaks, The hypothalamic-pituitary axis was postulated to be intact in these five patients, and all ovulated on clomiphene. None of the remaining five subjects showed any increase in serum gonadotrophin levels in response to oestradiol and none ovulated on clomiphene when given a dose of up to 200 mg daily x5 days. This 'oestrogen provocation test" seems to be a useful means of evaluating the functional capacity of the hypothalamic-pituitary axis for gonadotrophin release and has proved useful in predicting responsiveness to clomiphene in amenorrhoeic women.

Adult↗
PubMed1975

Sex hormone levels and gonadotrophin release in the polycystic ovary syndrome.

The response to synthetic luteinizing hormone-releasing hormone was studied in eighteen patients with the polycystic ovary syndrome. The release of follicle-stimulating hormone was similar to that found in normal women. The mean response of luteinizing hormone was similar to that found in the luteal phase, but significantly greater (P less than 0-02) than that found in the early follicular phase of the normal menstrual cycle. Basal serum levels of FSH and LH, estimated in twenty-five patients, were similar to those found in normal subjects. The sex hormone binding globulin capacity was reduced in twenty-four of them. Basal serum testosterone levels were elevated in twelve of twenty-two patients and the mean level was significantly greater (P less than 0-01) than the mean level of normal women. Basal serum androstenecione levels were elevated in nine of twenty-two patients and the mean level was also significantly greater (P leess than 0-001) between basal testosterone and LH levels. These data suggest the pituitary gland of patients with the polycystic ovary syndrome contains adequate amounts of LH but that the ovulatory surge of LH which occurs in normal women is inhibited by testosterone acting on either the pituitary or, more probably, on the hypothalamus.

Androstenedione↗
PubMed1975

The effect of oestrogen pretreatment on subsequent response to luteinizing hormone releasing hormone in normal women.

Twenty-two normal, regularly menstruating female subjects had an LHRH test performed before and after pretreatment with 0.5 mg, 1 mg. or 2.5 mg of oestradiol benzoate during the follicular phase of their menstrual cyclees (days 4-8). Two further women acted as controls and received no oestrogen; they showed identical responses for both LH and FSH release when LHRH tests were performed at intervals of 48 h. Oestrogen pretreatment induced a biphasic effect upon subsequent LHRH response. Four subjects retested 20 h after 0.5 mg oestradiol benzoate showed either no change or a slight suppression of LH and FSH release. Fifteen of the eighteen women pretreated with oestradiol benzoate and retested 44 h later showed significantly increased LH release and fourteen significantly increased FSH release when compared to their control responses. The responses appeared to be dose related with a positive correlation between sum of LH increments and basal oestradiol levels (R = 0.61; P less than 0.001) and a similar correlation (r = 0.67; P less than 0.001) between sum of FSH increments and basal oestradiol levels. The physiological significance of this biphasic action of oestrogen upon pituitary sensitivity is discussed in relation to the control of the menstrual cycle.

Adult↗
PubMed1975

The effect of progesterone and FSH and LH response to LHRH in normal women.

An LHRH test was performed on twenty-eight regularly menstruating females during follicular phase of their cycles. Twenty-four were then given an intramuscular injection of progesterone in oil and retested with LHRH 20 or 44 h later, the remaining four received no pretreatment and acted as controls. The twelve subjects retested 20 h after the progesterone injection showed marked changes in response. The greatest increase in gonadotrophin release after LHRH was seen when subjects were tested between days 8 and 10 of the menstrual cycle. In contrast, the twelve studied 44 h after receiving the steroid showed no change in release.

Adult↗
PubMed1975

Hypothalmic-pituitary relationships in the polycystic ovary syndrome serum gonadotrophin levels following injection of oestradiol benzoate.

Injection of oestradiol benzoate was found to elicit a surge of luteinizing hormone (LH) in 15 of 19 patients with polycystic ovary (PCO) syndrome; follicle stimulating hormone (FSH) was also released, in conjunction with the LH surge, in eight patients. It is concluded that the oestrogen feedback mechanisms controlling mid-cycle gonadotrophin release are functioning normally in the majority of patients with PCO syndrome. Ovulation was subsequently induced by clomiphene alone in those patients who had an LH surge, and by a combination of clomiphene and human chorionic gonadotrophin (HCG) in those who had not shown any LH release.

Amenorrhea↗
PubMed1975

Pathological mechanisms to explain some cases of amenorrhoea without organic disease.

A test is described to define the site of the lesion causing amenorrhoea in women of child-bearing age who have normal ovaries and a normal response to luteinizing hormone-releasing hormone (LH-RH). Patients able to produce a release of LH following the administration of 1 mg. of oestradiol benzoate (EB) have normal hypothalamic function and thus the site of the defect must lie more centrally in the brain. Patients unable to show these LH surges have either a primary or secondary abnormality affecting their hypothalamic oestrogen "receptor" mechanisms or their ability to produce LH-RH.

Amenorrhea↗