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Biomedical subjects

S Franks

Publications and source records attributed to S Franks.

At least 163 records · Page 9Linked to original sources
PubMed1985

Ovulatory disorders in women with polycystic ovary syndrome.

With the use of pelvic ultrasound imaging we have found that more than half of the women presenting to our clinic with ovulatory disturbances have polycystic ovaries. As a group hirsutism is common, the serum LH, the LH:FSH ratio and serum androgen levels are higher than in other groups of patients with anovulation, but many of the women we studied were non-hirsute and had normal levels of these hormones. The aetiology of PCOS remains obscure and there is probably more than one cause. Disturbance of hypothalamic/pituitary, ovarian or adrenal function could all result in the development of polycystic ovaries. Our own data, based on pelvic ultrasound and measurement of serum androgen levels, suggest that an ovarian abnormality, other than the obvious morphological one, may be identified in most women although this does not prove (except perhaps in those women with unilateral PCOS) that the ovary is the primary site of the disturbance. Management of ovulatory disturbances includes symptomatic treatment of dysfunctional uterine bleeding and induction of ovulation. Although the ovulation rate following clomiphene is quoted as about 75%, this is probably an overestimate; less than half the 'ovulators' become pregnant and in those who do there is a high risk of early pregnancy loss. Induction of ovulation in clomiphene non-responders remains a difficult problem. The results of ovarian wedge resection are variable and any beneficial effect is short-lived with the risk of long-term infertility due to pelvic adhesions. Laparoscopic electrocautery may be a useful alternative, but it is too early to assess this form of treatment. Of the medical methods of ovulation induction in clomiphene non-responders, two methods have emerged as being highly promising: the first is administration of HMG following suppression of the pituitary by an LH-RH analogue; so far only a very small number of patients have been treated. The second is low-dose FSH. Initial studies, including our own, have shown a high incidence of ovulation and a pregnancy rate of 50%.

Androgens↗
PubMed1984

Stimulation of prolactin secretion by oestradiol in the rat is associated with increased hypothalamic release of thyrotrophin-releasing hormone.

We have studied the effect of oestradiol (OE2) on secretion of prolactin and TSH by rat pituitary glands and correlated this with changes in hypothalamic content and release of thyrotrophin-releasing hormone (TRH). Ovariectomized Wistar rats received s.c. silicone elastomer implants of OE2 at a dose known to give pro-oestrous OE2 levels. After 1 week rats were decapitated, blood was collected for assay of prolactin and TSH, blocks of hypothalamus were dissected out and pituitary glands were removed and bisected. Medium bathing hemipituitary glands was collected for measurement of prolactin and TSH after a 30-min incubation. Immunoreactive TRH was measured in medium removed from hypothalami and in extracts of homogenized hypothalami. Serum prolactin was higher in OE2-treated than in control animals (59.3 +/- 19.5 (S.E.M.) vs 9.4 +/- 1.5 micrograms/l; P less than 0.05) and this was associated with a threefold increase in pituitary prolactin in the medium. By contrast, TSH concentrations in serum and pituitary incubation medium were not significantly different in the two groups. There was no difference between the groups in hypothalamic content of TRH but TRH release in the incubation medium was increased by OE2 (30.2 +/- 6.5 vs 10.0 +/- 1.3 pg/mg protein per 30 min; P less than 0.01). In summary, physiological levels of OE2 stimulated prolactin secretion without change in TSH and this was associated with a threefold increase in hypothalamic release of TRH. These findings suggest that the stimulating effect of OE2 on prolactin secretion may, in part, be mediated by hypothalamic TRH.

Animals↗
PubMed1983

Neurotensin regulation of TSH secretion in the rat.

Tri-iodothyronine stimulates neurotensin secretion from rat hypothalami in vitro. Propylthiouracil treatment of rats is associated with a decrease in anterior pituitary neurotensin content, an increase in hypothalamic content and an impaired release of peptide from hypothalami in vitro. In addition neurotensin has a direct inhibitory effect on TRH-stimulated TSH release from anterior pituitary in vitro. These observations suggest a physiological role for neurotensin in the control of TSH secretion in the rat.

Animals↗
PubMed1983

Effectiveness of pergolide mesylate in long term treatment of hyperprolactinaemia.

Twenty five patients with hyperprolactinaemia were treated with pergolide mesylate, a new dopamine receptor agonist. Twenty three received treatment for six to 20 months, and in all serum prolactin concentrations were considerably reduced. In most patients prolactin concentrations were maintained in the normal range by a low, once daily dose of pergolide and reversal of associated reproductive disorders was observed. Tumour volume as assessed by computed tomography decreased considerably during treatment in three out of four patients with a pituitary tumour. The drug was well tolerated. Side effects were similar to those of bromocriptine, but four out of eight patients who had been forced to stop taking bromocriptine because of untoward effects were subsequently able to tolerate treatment with pergolide. Pergolide mesylate promises to be a useful addition to the currently available long acting dopamine agonists in the management of hyperprolactinaemia.

Adult↗
PubMed1982

An acth-secreting pituitary tumour arising in a patient with congenital adrenal hyperplasia.

The case reported is of a 46-year-old woman who had congenital adrenal hyperplasia due to a 21-hydroxylase deficiency, and in whom there was the development of an ACTH secreting pituitary tumour. The patient was untreated with glucocorticoids until the age of 32 years when she presented with infertility. She next presented with amenorrhoea at the age of 44 years when she was found to have an enlarged pituitary fossa. Despite treatment with bromocriptine and adequate doses of dexamethasone, the tumour enlarged and required operative treatment 1 year later. Before and after operation, plasma ACTH levels were between 300 and 400 ng/l, immunocytochemistry showed staining for ACTH and other structurally related pro-opiocortin peptides but for no other hormones, and the tumour secreted large amounts of ACTH in vitro. The report of this case is to our knowledge the first account of a feedback tumour in congenital adrenal hyperplasia and provides yet another reason why patients with this condition should be treated, and good control achieved.

Adenoma, Basophil↗
PubMed1982

Comparative pharmacology of oestrogens and catechol oestrogens: actions on the immature rat uterus in vivo and in vitro.

The effects of primary and catechol oestrogens on the uterus of the immature rat were compared. Because differences between the in-vivo and in-vitro oestrogenic actions of catechol oestrogens on the secretion of LH had been observed, their effects on a peripheral target organ, the uterus, were examined under similar conditions. In-vivo effects were assessed by measurement of uterine weight, induction of uterine cytoplasmic progestogen receptors, and by histological examination. In-vitro actions were determined by measurement of oestrogen-specific induced protein. It was found that the uterotrophic effects in vivo of 4-hydroxyoestradiol were indistinguishable from those of oestradiol whereas 2-hydroxyoestradiol was only weakly oestrogenic and 2-hydroxyoestrone had no effect. However, in vitro, 2-hydroxyoestradiol was as effective as 4-hydroxyoestradiol or oestradiol in stimulating synthesis of uterine induced protein, and 2-hydroxyoestrone, although less potent than oestradiol, had a significant effect. These results were consistent with the observed effects on the secretion of LH. The differences between in-vivo and in-vitro uterotrophic properties of catechol oestrogens can be explained on the basis of known pharmacokinetic factors.

Animals↗
PubMed1981

Treatment of hyperprolactinaemia with pergolide mesylate: acute effects and preliminary evaluation of long-term treatment.

The acute and long-term effects of oral pergolide mesylate, a new potent, long-acting dopamine agonist, were investigated in 10 hyperprolactinaemic patients. After a single 50 micrograms dose of pergolide mesylate, serum prolactin concentrations fell steadily to reach a mean minimum value at 6 h of 20% of baseline values; this degree of suppression was maintained throughout the 24 h study period. In one patient serum prolactin was measured for 2 days after a single dose and remained suppressed for 45 h. There were no acute changes in the serum concentration of luteinising hormone, follicle-stimulating hormone and growth hormone. Preliminary evaluation of longer term treatment with pergolide indicates that this drug at a once-daily dose of 50-150 micrograms is a safe, well tolerated, and effective new treatment for hyperprolactinaemia.

Administration, Oral↗
PubMed1981

Failure of 2-hydroxyoestrone to lower prolactin concentrations in hyperprolactinaemic women.

The catechol oestrogen 2-hydroxyoestrone has been reported to lower serum prolactin concentrations acutely in normal women and it has been proposed that it may be effective in suppressing prolactin secretion in hyperprolactinaemic patients. Five women with hyperprolactinaemia and anovulation were studied. Following a control infusion, 2-hydroxyoestrone was given at a rate of 80 micrograms/h for 4 h. In no patient was there a fall in prolactin levels and no changes were observed in gonadotrophin concentrations. We conclude that a short-term infusion of 2-hydroxyoestrone, at a dose which will produce high blood levels of the steroid, does not affect prolactin or gonadotrophin secretion in hyperprolactinaemic states.

Adult↗
PubMed1981

Actions of catechol oestrogens on concentrations of serum luteinizing hormone in the adult castrated rat: various effects of 4-hydroxyoestradiol and 2-hydroxyoestradiol.

The pharmacological effect of 2-hydroxyoestradiol (2-OHE2) and 4-OHE2 on concentrations of LH in the chronically castrated rat have been compared with that of oestradiol in order to determine whether the in-vivo activity is altered by insertion of a hydroxyl group at position 2 or 4 of the aromatic A ring; these derivatives are naturally occurring oestrogen metabolites. Four groups of six adult male rats were used 4 weeks after bilateral orchidectomy. The right jugular vein was exposed under ether anaesthesia and a basal blood sample taken (10.00 h) immediately before an intravenous injection of vehicle alone (0.1 ml ethanol with 0.01% ascorbic acid), oestradiol, 2-OHE2 or 4-OHE2 (10 micrograms of each in 0.1 ml vehicle). Blood was taken from each animal at 2, 4, 6, 8 and 24 h after treatment and serum assayed for LH. Baseline LH levels were similar in the four groups. At 2 h there was no change in 2-OHE2-treated rats but there was a significant decrease of serum levels of LH in rats treated with oestradiol and 4-OHE2 compared with vehicle-treated controls. The decrease in LH was quantitatively similar in oestradiol- and 4-OHE2-treated groups and was sustained at 4, 6 and 8 h, returning to control values at 24 h. In subsequent experiments the effects of lower doses of these two steroids were compared and the potency of 4-OHE2 was estimated to be about 25% that of oestradiol. In a further experiment, 2-OHE2 (100 micrograms) had no effect when given alone, but when injected i.v. immediately before treatment with 1 microgram oestradiol, it was able to inhibit the suppression of LH by oestradiol. In conclusion, 4-OHE2 had a potent effect in lowering plasma LH levels whereas 2-OHE2, even at a high dose (100 micrograms), did not suppress LH but it was able to inhibit the effect of oestradiol. These differences in biological activity may reflect more rapid metabolism of 2-OHE2 or differences in binding properties of these catechol oestrogens to the oestrogen receptor.

Animals↗
PubMed1981

Stimulation of release of luteinizing hormone from cultured pituitary cells by 2- and 4-hydroxylated oestrogens.

We have examined the effect of the catechol oestrogens 2-hydroxyoestradiol (2-OHE2), 4-hydroxyoestradiol (4-OHE2) and 2-hydroxyoestrone (2-OHE1) and their corresponding primary oestrogens on secretion of LH and FSH by enzymatically dispersed rat anterior pituitary cells in monolayer culture. Basal LH levels in the medium were significantly higher than in control wells when cells were exposed to 10(-8) M-oestradiol-17 beta for 40 h: oestrone and all three catechol oestrogens (in the same doses) also stimulated basal LH concentrations to levels quantitatively similar to those seem after oestradiol treatment. The same effects were observed when steroids were given at 10(-9) mol/l. Oestradiol, 2-OHE2, and 4-OHE2 but not 2-OHE1 increased pituitary responsiveness to LH releasing hormone (LH-RH) (given in a range of doses from 10(-11) to 10(-6) mol/l). The responses of cells treated with 2-OHE2 and 4-OHE2 were similar, though less than the response seen after treatment with oestradiol. This contrasts with the very different oestrogenic effects of 2- and 4-OHE2 previously observed in vivo. Neither oestradiol nor the catechol oestrogens had any effect on basal or LH-RH-stimulated FSH release.

Animals↗
PubMed1980

Breast examination does not elevate serum prolactin.

Serum prolactin and cortisol levels were measured in 24 patients entering the Royal Victoria Hospital infertility center both before and after a thorough physical examination that included a pelvic examination and a search for galactorrhea in both breasts. There was no significant change in the levels of prolactin or cortisol in the group as a whole in those with normal prolactin values and those with high basal prolactin values (P less than 0.05). The possible role of stress in the mediation of occasional elevation of basal prolactin values is discussed in relation to the serum cortisol levels.

Adenoma↗