Search PubMed⌕ Search

Biomedical subjects

S Franks

Publications and source records attributed to S Franks.

At least 145 records · Page 8Linked to original sources
PubMed1988

Androstenedione concentrations following dexamethasone suppression: correlation with clomiphene responsiveness in women with polycystic ovary syndrome.

It is difficult to predict clomiphene responsiveness in women with polycystic ovary syndrome (PCOS) but it has been suggested that women with evidence of excess adrenal androgen are less likely to respond to clomiphene. To investigate this further we performed a short Synacthen test following overnight dexamethasone suppression, using 11 beta-hydroxyandrostenedione (11-OHA) as a specific marker of adrenal androgen secretion in women with anovulatory infertility due to PCOS (n = 19) compared with a normal group (n = 7). Women with PCOS were subsequently divided into 2 groups according to whether or not they ovulated after clomiphene. On day 1 blood was taken at 9.00 hours for measurement of androstenedione (A), 11-OHA and cortisol, and 1 mg dexamethasone was given at 22.00 hours. On day 2 blood was taken at 9.00 hours and at 30 and 60 minutes after intravenous administration of 250 micrograms Synacthen. Before dexamethasone was given, concentrations of A but not of 11-OHA or cortisol were significantly higher in women with PCOS than in controls but there was no difference in A levels between clomiphene responders and non-responders. After 1 mg dexamethasone had been given, concentrations of A, 11-OHA and cortisol were suppressed in all 3 groups and there were no differences between the groups in the post-dexamethasone concentrations of 11-OHA or cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Amenorrhea↗
PubMed1987

Modulation of phospholipase A2 activity in human endometrium and amniotic membrane by steroid hormones.

Phospholipase A2 (PLA2) activity was measured in endometrium and amnion by a double isotope ratio technique using 1-palmitoyl-2-oleoyl phosphatidylcholine as substrate in the presence and absence of a range of unconjugated steroids and steroid sulphates (0.2-6.4 X 10(-4) M). In the presence of 0.1% Triton, PLA2 activity was inhibited by the majority of steroids tested, pregnenolone sulphate being the most effective (12.9 +/- 3.0% control activity) while oestradiol sulphate, oestrone and testosterone had only a minimal or no effect (99.1 +/- 19.0, 85.4 +/- 4.4 and 104.2 +/- 16.3% control respectively). In the absence of Triton, the inhibitory effect of the free steroids was reduced or absent but oestradiol sulphate and testosterone sulphate stimulated activity by 2-13 and 1.5-3 times respectively. The effect was dose related, linear with time and independent of the stage of the menstrual cycle. Inhibition by pregnenolone sulphate, dehydroepiandrosterone (DHA sulphate and oestrone sulphate was maintained in the absence of Triton (24.9 +/- 3.8, 67.1 +/- 10.1 and 87.2 +/- 13.8% control respectively). In amnion all 5 steroid sulphates caused a marked stimulation of PLA2 activity in both the presence and absence of Triton. The effect was greatest without Triton and at 6.4 X 10(-4) M, testosterone, pregnenolone, oestrone, DHA and oestradiol sulphates increased PLA2 activity 20, 15, 12, 10 and 6-fold respectively. These findings indicate a direct action of steroid sulphates on PLA2 activity in endometrium and amnion.

Amnion↗
PubMed1987

Endometrial phospholipase A2 enzymes and their regulation by steroid hormones.

The presence of two phospholipase A2 (PLA2) enzymes, designated PLA2(i) and PLA2(ii), has been demonstrated in human endometrium. These enzymes differ with respect to pH and calcium requirements, location within the tissue and regulation by steroid hormones. Phospholipase A2(i) is calcium dependent, optimally active at pH 7.5-9.0 and present mainly in the glandular component of the endometrium. Changes in activity occur during the menstrual cycle which are indicative of regulation by ovarian steroids. Conversely, PLA2(ii) is calcium independent, optimally active at pH 7.0 and located predominantly in the stromal layer. Wide variation in PLA2(ii) activity was found between individual subjects and there was no relationship with the stage of the menstrual cycle. Activity was, however, much higher in pathological endometrium and in endometrium from subjects with severe dysmenorrhoea. Triton X-100 activated PLA2(i) but not PLA2(ii). In cultured explants of endometrium, both enzymes were inhibited by progesterone whereas oestradiol and dexamethasone had no effect. However, progesterone priming followed by treatment with oestradiol caused a 2-fold stimulation of PLA2(i) but not PLA2(ii). Phospholipase A2 is favoured as the rate-limiting step in the generation of arachidonic acid for prostaglandin synthesis. However, our studies so far do not support a direct relationship between PLA2 and endometrial concentrations of prostaglandins, which implies that other important regulatory steps are involved. Other enzymes which are potentially capable of mobilizing arachidonic acid should also be investigated.

Calcium↗
PubMed1987

Bromocriptine treatment of women with clomiphene-resistant polycystic ovary syndrome.

Twenty-three patients with polycystic ovary syndrome and anovulatory infertility have been treated with bromocriptine. All had previously failed to respond to clomiphene. Twenty had normal serum prolactin concentrations and, of these, four (20%) developed regular ovulatory cycles. All three women with moderate hyperprolactinaemia ovulated regularly on bromocriptine so that, overall, seven of 23(30%) responded, which was a significantly higher proportion than that observed during a control period of no treatment. A further eight women ovulated at least once during the study period but these occasional ovulations were no more common during bromocriptine than with either clomiphene or no treatment. No suppression of LH was noted except during the luteal phase of ovulatory cycles and there was no change in the pattern of pulsatile release of LH. Testosterone and androstenedione concentrations remained elevated and unchanged. We conclude that bromocriptine may be expected to induce ovulation in hyperprolactinaemic women with polycystic ovary syndrome but that there is no clear indication for its use in clomiphene-resistant patients with normal serum prolactin concentrations.

Adult↗
PubMed1987

Ovulation of a single dominant follicle during treatment with low-dose pulsatile follicle stimulating hormone in women with polycystic ovary syndrome.

Ten women with clomiphene-resistant chronic anovulation associated with polycystic ovary syndrome were treated with purified urinary FSH (urofollitrophin). The gonadotrophin was given s.c. by pulsatile infusion pump starting at a low dose (1 ampoule or 75 U/d) and increasing by 37.5 U/d at weekly stages in an attempt to induce ovulation of a single follicle. Seventy percent of the 33 cycles were ovulatory and in 18 of these (78%) a single dominant follicle developed and ovulated. Each of the 10 women ovulated when the optimum dose was reached and five of these women became pregnant. The maximum dose of FSH in uni-ovulatory cycles was 150 U/d or less. Endogenous LH concentrations which were raised at the onset of treatment were suppressed in the late follicular phase. The rate of follicular growth and gonadal steroid concentrations were consistent with those observed in spontaneous ovulatory cycles. This study demonstrates that by using low-dose gonadotrophin therapy it is possible to find the 'threshold' dose of FSH to promote maturation of a single dominant follicle. The high rate of ovulation and pregnancy suggest that this approach is of practical importance in treatment of infertile patients with polycystic ovaries.

Adult↗
PubMed1987

The distribution of oestradiol in plasma in relation to uterine cross-sectional area in women with polycystic or multifollicular ovaries.

The uterine cross-sectional area (UXA) of women with polycystic (PCO) or multifollicular ovaries (MFO) is significantly larger and smaller, respectively, than those of normal women during the early-mid-follicular phase of the menstrual cycle. In the present study the distribution of oestradiol in plasma from normal women and women with PCO or MFO was measured to determine if differences in the available fractions of oestradiol could account for the differences in UXA of women with PCO or MFO. No differences in plasma levels of oestradiol were detected and the concentrations of oestradiol present in a free state or bound to albumin were similar in normal women and women with PCO or MFO. The concentration of oestrone was significantly higher in plasma from women with PCO (516 +/- 120 pmol/l, mean +/- SD) than in plasma from women with MFO (389 +/- 91 pmol/l) or normal women (376 +/- 89 pmol/l). Differences in UXA for women with PCO or MFO as compared with normal women cannot therefore be attributed to differences in available oestradiol concentrations. It is possible that abnormalities in oestrogen metabolism within uterine or other tissues may account for the UXA of women with PCO or MFO. Increased plasma oestrone levels in women with PCO may provide more substrate for conversion to oestradiol within the uterus whilst the smaller UXA of women with MFO may reflect both lack of normal cyclical increases of oestradiol and formation of biologically inactive oestradiol metabolites.

Body Constitution↗
PubMed1987

Recovery of luteal function after interruption of gonadotrophin secretion in the mid-luteal phase of the menstrual cycle.

Ovulation was induced by a pulsatile infusion of GnRH in a patient with hypogonadotrophic amenorrhoea. In order to investigate the effect of short-term withdrawal of gonadotrophin support in the luteal phase, the pulsatile infusion was stopped 3 d after ovulation and restarted 48 h later. After stopping the pump gonadotrophin and progesterone concentrations fell rapidly to very low levels, but when the infusion was restarted progesterone concentrations returned to normal mid-luteal values. Menstruation occurred 14 d after the LH surge. We conclude that normal progesterone secretion by the corpus luteum can be restored after temporary withdrawal of gonadotrophin support.

Amenorrhea↗
PubMed1987

Phospholipase C activity in human endometrium: its significance in endometrial pathology.

Phospholipase C activity was measured in human endometrium using an assay based on the release of total labelled water soluble products (inositol, inositol phosphates) from L-3-phosphatidyl-[2-3H] inositol. The enzyme was shown to be calcium dependent and to have an optimum pH of 5.5. There was no difference between proliferative phase and secretory phase endometrium with respect to phospholipase C activity either in women with normal menstrual blood loss (proliferative phase: 3.7 +/- 0.7 (mean +/- SD), secretory phase: 4.5 +/- 2.0 nmol/mg protein/min) or in those complaining of severe menorrhagia (proliferative phase: 5.8 +/- 2.8, secretory phase: 7.0 +/- 2.8 nmol/mg protein/min). However, women complaining of severe menorrhagia had significantly higher endometrial phospholipase C activity than those in the normal group (P less than 0.01 and P less than 0.02 for proliferative and secretory phases respectively). Endometrial phospholipase C activity was also elevated in the presence of other gynaecological disorders, e.g. dysmenorrhoea, adenocarcinoma of the cervix and endometrial hyperplasia. The results indicate that phospholipase C activity in human endometrium is not related to the stage of the menstrual cycle but that in the presence of menorrhagia and other gynaecological disorders, activity is increased. Phospholipase C could be implicated in the generation of arachidonic acid for prostaglandin synthesis which may in turn be associated with these abnormalities.

Adult↗
PubMed1987

Use of LHRH agonists in the treatment of anovulation in women with polycystic ovary syndrome.

The long-acting agonist analogue of LHRH, Buserelin (Hoechst) has been used to suppress endogenous gonadotrophins prior to induction of ovulation with low dose human menopausal gonadotrophin (HMG) in women with clomiphene-resistant polycystic ovary syndrome (PCOS). The results have been compared with those in a similar group of patients treated with HMG alone. Buserelin (900-1,500 micrograms/day) was given intranasally to 11 women who thereafter received a total of 33 cycles of treatment with low-dose HMG. The control group comprised 16 women who received 40 cycles of HMG without Buserelin pretreatment. The ovulation rate was similar in the two groups: Buserelin + HMG 70%, HMG alone 68% and both groups showed a high rate of single follicle ovulation (52 and 63%, respectively). The threshold dose of gonadotrophin required to induce a single follicle was similar in the two groups. Premature elevation of LH in the late follicular phase was common in women who received HMG alone, but did not occur in any cycle in the patients receiving Buserelin pretreatment. In summary, these data show that pretreatment with an LHRH analogue prevents a premature LH surge but it remains to be determined whether this will have a significant bearing on the rate of successful pregnancy in women with PCOS.

Anovulation↗
PubMed1986

Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism.

Polycystic ovaries were defined with ultrasound imaging in a series of 173 women who presented to a gynaecological endocrine clinic with anovulation or hirsutism. Polycystic ovaries were found in 26% of women with amenorrhoea, 87% with oligomenorrhoea, and 92% with idiopathic hirsutism--that is, hirsutism but with regular menstrual cycles. Fewer than half the anovulatory patients with polycystic ovaries were hirsute, but in 93% of cases there was at least one endocrine abnormality to support the diagnosis of polycystic ovaries--that is, raised serum concentrations of luteinising hormone, raised luteinising hormone: follicle stimulating hormone ratio, or raised serum concentrations of testosterone or androstenedione. This study shows that polycystic ovaries, as defined by pelvic ultrasound, are very common in anovulatory women (57% of cases) and are not necessarily associated with hirsutism or a raised serum luteinising hormone concentration. Most women with hirsutism and regular menses have polycystic ovaries so that the term "idiopathic" hirsutism no longer seems appropriate.

Androstenedione↗
PubMed1986

The regulation of the biologically available fractions of oestradiol and testosterone in plasma.

The albumin bound fractions of oestradiol and testosterone have been measured in samples of plasma obtained over a 24 h period from women with breast cancer or polycystic ovarian disease and from pre- and postmenopausal control subjects and related to plasma levels of free fatty acids. For most subjects changes in the fraction of oestradiol bound to albumin were related to changes in plasma levels of free fatty acids. A significant decrease in the albumin bound testosterone fraction during the night was associated with increased plasma levels of cortisol.

Biological Availability↗
PubMed1986

The effect of glucocorticoids on the in vivo conversion of androstenedione to oestrone.

In vitro studies have previously shown that the activity of the aromatase enzyme system, which is responsible for the conversion of androstenedione to oestrone, can be stimulated by natural and synthetic glucocorticoids and also by ACTH. In view of the potential physiological importance of such a regulatory mechanism we have examined the effect of administration of dexamethasone, and of ACTH on the conversion of androstenedione to oestrone in vivo. The transfer constants for the conversion of androstenedione to oestrone [( rho]AEBU) measured in two women before administration of dexamethasone were 1.0% and 1.1% and after were 0.9% and 1.2%. Similarly no increase in conversion of androstenedione to oestrone [( rho]AE1BB) was detected after ACTH stimulation (pre = 0.74%, post = 0.77%). It is concluded from this study that glucocorticoids and ACTH do not have a role in regulating aromatase activity in vivo.

Adrenocorticotropic Hormone↗
PubMed1986

Ovulation and normal luteal function during LHRH treatment of women with hyperprolactinaemic amenorrhoea.

Five patients with hyperprolactinaemic amenorrhoea who had been resistant to, or intolerant of bromocriptine were treated with pulsatile LHRH therapy. Ovulation was induced in 9 of 12 treatment cycles. In one patient hyperstimulation occurred in the first cycle of treatment but subsequently she ovulated normally on a reduced dose of LHRH. The gonadotrophin and ovarian responses to treatment in ovulatory cycles were normal despite prolactin concentrations that remained elevated throughout treatment and rose still further with resumption of ovarian activity. The length of the luteal phase and the mid-luteal serum progesterone concentrations were also normal. Pulsatile secretion of progesterone in response to LHRH pulses were observed. These data show that ovulation and normal luteal function can be induced by physiological LHRH replacement in women with persistent hyperprolactinaemia. This confirms that the mechanism of anovulation in hyperprolactinaemic amenorrhoea is disordered LHRH secretion.

Adult↗
PubMed1986

Assays for prolactin: guidelines for the provision of a clinical biochemistry service.

This paper summarises the views of the authors on the provision of a prolactin assay service. We discuss the pathophysiology of prolactin secretion and the clinical indications that arise from that. We cover the rather complex issue of the definition of normal and elevated prolactin levels. From these considerations, certain guidelines on the analytical performance of prolactin assays and their provision in a clinical biochemistry service are given. The extent to which currently available methods and performance as revealed by the UK External Quality Assessment Scheme (EQAS) match these guidelines are described and certain conclusions are reached. Finally, probable future developments are briefly discussed. The main conclusions and recommendations are as follows: Reagents of appropriate quality are available to enable prolactin immunoassays to be provided in UK clinical biochemistry laboratories. These are provided either separately or in the form of kits from both commercial and NHS sources. There is no requirement for individual laboratories to undertake their own antiserum production or prolactin iodination. Acceptable performance (as defined using internal QC procedures and the UK EQAS) is achievable using these reagents/kits, although one commercial kit shows a consistent marked negative bias. Reference ranges, including 'normal ranges', show considerable between-centre variability. Many centres have not established their own ranges, even those using in-house methods. Reference ranges for use in clinical biochemistry laboratories are proposed in this report. Some general guidance on the provision of a prolactin service is given, although this does not differ in principle from that appropriate for other peptide hormone analytes. There is no evidence that centres with small workloads perform any worse than average, although it may be more cost-efficient for such centres to send the samples elsewhere. As with other peptide analytes, non-isotopic immunometric methodology is likely to replace current radioimmunoassay methods in the near future.

Female↗
PubMed1986

The dopaminergic regulation of anterior pituitary 45Ca2+ homeostasis and prolactin secretion.

A role for the regulation of cellular Ca2+ homeostasis in the dopaminergic control of prolactin secretion was investigated in rat anterior pituitary glands. Withdrawal of dopamine stimulated the uptake of 45Ca2+ into hemipituitary tissue by 48% after 3 min. Radioisotope desaturation from tissue prelabelled with 45Ca2+ was significantly retarded in the presence of dopamine. Withdrawal of dopamine rapidly stimulated 45Ca2+ efflux from prelabelled tissue by 79% and was accompanied by a three- to fourfold rise in prolactin secretion. The 45Ca2+ efflux response to dopamine withdrawal was reduced in tissue prelabelled in the presence of dopamine. Agonist displacement with metoclopramide mimicked the effect of dopamine withdrawal on 45Ca2+ efflux and prolactin secretion. These observations demonstrate that the stimulation of prolactin release by dopamine withdrawal is accompanied by a redistribution of cellular Ca2+ and support the hypothesis that dopamine inhibits secretion by decreasing Ca2+ influx in the mammotroph cell.

Animals↗