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P Morley

Publications and source records attributed to P Morley.

At least 127 records · Page 7Linked to original sources
PubMed1989

Insulin enhances luteinizing hormone-stimulated steroidogenesis by porcine theca cells.

It has been shown recently that insulin enhances differentiation of rat, pig, and human granulosa cells. The present studies were done to determine if insulin also plays a role in the regulation of theca cell steroidogenesis. Theca cells were obtained from prepubertal gilts and cultured under serum-free conditions for 48 h. Theca cell androstenedione production under basal and luteinizing hormone (LH)-stimulated conditions was significantly increased by adding insulin (1 microgram/ml) to the culture medium. Treatment of basal and LH-stimulated cultures with increasing concentrations of insulin (0.001-10 micrograms/ml) caused dose- and time-dependent increments in androstenedione production, but the effect was independent of the dose of LH employed. The ability of insulin to enhance thecal cell androstenedione production was mimicked by somatomedin C, but not by relaxin. Studies to determine the mechanism(s) of action of insulin showed that insulin action is exerted, at least in part, at a site(s) proximal to cyclic adenosine 3'5'-monophosphate (cAMP) generation, since insulin enhanced both basal and LH-stimulated accumulation of extracellular cAMP in addition to increasing androstenedione production. This effect was further enhanced by 3-isobutyl-1-methyl xanthine, an inhibitor of phosphodiesterase activity. Insulin treatment also caused dose-dependent increments in forskolin- and prostaglandin E2-stimulated accumulation of extracellular cAMP and androstenedione. Insulin also increased both the basal and LH-stimulated production of progesterone and its precursor pregnenolone, in addition to the increases in androstenedione.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1989

Catecholestrogens inhibit basal and luteinizing hormone-stimulated androgen production by porcine thecal cells.

It has been shown recently that catecholestrogens are produced by cultured porcine granulosa and thecal cells, and that they influence porcine granulosa cell steroidogenesis in a similar manner to estradiol-17 beta (E2). The present studies were performed to determine if catecholestrogens also play a role in the regulation of porcine thecal cell steroidogenesis and to compare their actions to those of E2. Thecal cells were obtained from prepubertal gilts and cultured in a serum-free medium for 48 h. Thecal cell androstenedione production under basal and luteinizing hormone (LH)-stimulated conditions was significantly inhibited by adding E2 or catecholestrogens to the culture medium. Treatment of basal and LH-stimulated cultures with increasing concentrations of E2 or catecholestrogens (0.1-10 micrograms/ml) caused a dose-and time-dependent inhibition of androstenedione production. The inhibitory effect of the catecholestrogens, but not of E2, was enhanced when the cultures contained the catechol-O-methyl transferase inhibitor, U-0521. Studies to determine the mechanism(s) of action of the catecholestrogens showed that E2 and catecholestrogen actions are exerted at a site(s) distal to cyclic adenosine 3'5' monophosphate (cyclic AMP) generation, because neither agent affected the basal or LH-stimulated accumulation of extracellular cyclic AMP, while causing a significant inhibition of androstenedione production. E2 or catecholestrogen treatment also inhibited androstenedione production stimulated by prostaglandin E2 and dibutyryl cyclic AMP. In addition, both E2 and catecholestrogen treatment significantly decreased basal and LH-stimulated 17 alpha-hydroxyprogesterone production, while significantly increasing pregnenolone production. Progesterone production in the presence of E2 or catecholestrogens showed small but statistically insignificant increases.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1989

Ovarian nerve extracts influence androgen production by cultured ovarian thecal cells.

There is growing evidence that ovarian steroidogenesis is controlled not only by pituitary gonadotropins but also by ovarian nerves. Nerves reach the ovary via the plexus nerve and via the superior ovarian nerve (SON), which runs in the suspensory ligament, and innervate theca cells of all sizes of follicles. To investigate the role of ovarian nerves in steroidogenesis we have examined the effects of adding an extract of SON from adult rats on androgen production by cultured porcine theca cells. Addition of SON extract to cultured theca interna from 3 to 6 mm diameter follicles of prepubertal gilts significantly inhibited (p less than 0.05) LH-stimulated androstenedione production in a dose-dependent manner; significant inhibition (10.8%) occurred with the addition of the extract of 2 mg of SON/ml culture medium, and near maximal inhibition (83%) resulted when the SON extract was increased to 60 mg SON/ml. Extracts of sciatic nerves, used as non-ovarian nerve controls, failed to inhibit, and in fact significantly increased (p less than 0.05) androstenedione production over the same concentration range of neural tissue extract. The inhibitory effect of the SON extract was unaffected by chymotrypsin digestion or by the presence of the beta-adrenergic antagonist propranolol (10(-6) M), but was removed by charcoal treatment. These results suggest that the nervous system has the potential for modulation of follicular steroid biosynthesis via direct innervation of the ovaries, in addition to the well-established indirect mechanism of neural control exerted via the hypothalamic-pituitary system.

Adipose Tissue↗
PubMed1989

Ultrasound in suspected obstruction complicating renal transplantation.

The findings of regular ultrasound examination of 439 renal transplants in 419 patients performed during a 16-year period were reviewed to determine the significance of collecting system dilatation. Dilatation was observed in 80 cases. 34 of these proving to be obstructed. Pelvic dilatation was an insignificant finding except when appearing within a month of transplantation. One third of cases developing pelvic dilatation within a month showed progressive dilatation with obstruction subsequently confirmed. The majority of cases developing unheralded dilatation of pelvis and calyces were obstructed and all such patients require further investigation. Recurrence of dilatation following relief of obstruction was associated with recurrent obstruction in eight of nine cases. Consideration of ultrasound appearances allows more critical selection of patients for further investigation when dilatation is seen.

Dilatation, Pathologic↗
PubMed1989

Formation of 4-oestrene-3,17-dione (19-norandrostenedione) by porcine granulosa cells in vitro is inhibited by the aromatase inhibitor 4-hydroxyandrostenedione and the cytochrome P-450 inhibitors aminoglutethimide phosphate and ketoconazole.

The origin and biosynthesis of 4-oestrene-3,17-dione (19-norandrostenedione), a major steroid in porcine ovarian follicular fluid, was investigated by culturing granulosa cells from 4-6 mm follicles of prepubertal gilts with radiolabelled androstenedione and 19-hydroxyandrostenedione. Steroid metabolites were purified by solvent extraction and lipophilic column chromatography, and analysed by C18 reverse-phase high-performance liquid chromatography. 19-Hydroxyandrostenedione, 19-norandrostenedione and oestradiol-17 beta were obtained as major metabolites from androstenedione, while 19-norandrostenedione and oestradiol-17 beta were the major products from 19-hydroxyandrostenedione. Serum alone or serum plus FSH significantly enhanced formation of 19-norandrostenedione and oestradiol-17 beta from each substrate, compared with controls. Micromolar concentrations (1 mumol/l) of 4-hydroxyandrostenedione, an aromatase inhibitor, significantly reduced formation of 19-norandrostenedione and oestradiol-17 beta by granulosa cells cultured with serum and FSH. Formation of 19-norandrostenedione and oestradiol-17 beta from androstenedione and 19-hydroxyandrostenedione was also significantly inhibited by aminoglutethimide phosphate, a cytochrome P-450 inhibitor known to block the conversion of androstenedione to oestrogens. Ketoconazole, an inhibitor of the cytochrome P-450 dependent 17,20-lysase, blocked formation of 19-norandrostenedione and oestradiol-17 beta only at millimolar concentrations. These results suggest that 19-norsteroid and oestrogen formation from C19 aromatizable androgens may share a common or overlapping pathway, and imply that 19-norsteroid and oestrogen synthesis is mediated by cytochrome P-450 dependent enzymes.

Aminoglutethimide↗
PubMed1988

Formation and metabolism of 5(10)-estrene-3 beta,17 beta-diol, a novel 19-norandrogen produced by porcine granulosa cells from C19 aromatizable androgens.

The biosynthesis of non-aromatic 19-norsteroids has been studied using primary cultures of porcine granulosa cells. Formation of 5(10)-estrene-3 beta,17 beta-diol, a novel 19-norsteroid, from androstenedione and 19-hydroxyandrostenedione by porcine granulosa cells is reported for the first time. The structure was deduced from (i) comparison of its elution times on C18 reverse phase HPLC with authentic 5(10)-estrene-3 beta,17 beta-diol (ii) identification with 5(10)-estrene-3 beta,17 beta-diol-diacetate after acetylation (iii) oxidation/acid catalysed isomerization to 19-norandrostenedione. Serum or serum plus FSH significantly stimulated (seven fold increase) formation of 5(10)-estrene-3 beta,17 beta-diol from androstenedione and 19-hydroxyandrostenedione. Formation of 5(10)-estrene-3 beta,17 beta-diol from both substrates was significantly (p less than 0.01) reduced by the aromatase inhibitors 4-hydroxyandrostenedione (15 microM) and aminoglutethimide phosphate (10(-4)M). These results suggest that 5(10)-estrene-3 beta,17 beta-diol (and 19-norandrostenedione) may be formed by enzymes similar to the aromatase complex required for estradiol-17 beta biosynthesis. 5(10)-Estrene-3 beta,17 beta-diol is converted by granulosa cells to four metabolites. 19-Norandrostenedione was identified by crystallization to constant specific activity; 19-nortestosterone is a minor product. Production of 19-norandrostenedione and 19-nortestosterone indicates that granulosa cells possess the enzymes necessary for the transformation of 5(10)-estrene-3 beta,17 beta-diol and other 3-hydroxy-5(10)-estrenes to 19-nor-4-ene-3-ketosteroids. The formation of 5(10)-estrene-3 beta,17 beta-diol and 19-norandrostenedione as substantial metabolites of androstenedione suggest a physiological role for these 19-norsteroids in ovarian follicular development.

Acetylation↗
PubMed1988

Overnight clonidine suppression test in the diagnosis and exclusion of pheochromocytoma.

In a prospective study designed to differentiate pheochromocytoma from other forms of hypertension, urinary catecholamines were measured after sleep and clonidine administration in 12 patients with pheochromocytoma, 19 hypertensive patients in whom pheochromocytoma was suspected but later excluded, and 31 hypertensive patients in whom pheochromocytoma was never suspected. The test correctly identified all 12 patients in whom pheochromocytoma was present. Four of these had equivocal plasma levels of both norepinephrine and epinephrine, suggesting that overnight clonidine suppression may be of particular value when tumor secretion is intermittent or low. When pheochromocytoma was not present, urinary norepinephrine and epinephrine levels were suppressed below 60 and 20 nmol/mmol creatinine, respectively, after sleep and clonidine, the two in combination giving better suppression than sleep alone. Since urinary catecholamines can be determined relatively easily by high-pressure liquid chromatography with electrochemical detection, this test may be more widely applicable than suppression tests based on plasma measurements.

Adrenal Gland Neoplasms↗
PubMed1987

Fibronectin stimulates growth but not follicle-stimulating hormone-dependent differentiation of rat granulosa cells in vitro.

Since fibronectin is a secretory product of immature rat granulosa cells in culture and may contribute to the follicular microenvironment in vivo, we have studied the effects of this adhesion factor on follicle-stimulating hormone (FSH)-dependent differentiation in short-term (2-3-day) cultures and on growth and protein synthesis in long-term (12-day) cultures. In comparison with cells plated on tissue culture plastic, those plated on an optimal fibronectin-coated substratum showed much greater cell spreading. There were no short-term effects of this morphological change on FSH-stimulation of cyclic AMP production, apparent activities of aromatase or cholesterol side-chain cleavage enzymes, or acquisition of luteinizing hormone (LH) responsiveness in cultured cells. However, progesterone metabolism to 20 alpha-hydroxypregnan-4-en-3-one was increased. Only cultures on fibronectin showed increases between days 3 and 9 in protein (2.5-fold) and DNA (1.4-fold) contents. Cells cultured on fibronectin also showed greater uptake and incorporation of [3H]leucine in comparison with cells cultured on plastic. FSH treatment caused cell aggregation and rounding and delayed the increase in protein content of cells cultured on fibronectin. The results presented demonstrate that the principal direct effect of fibronectin-mediated adhesion on rat granulosa cells is to enhance cell maintenance and growth, while having no generalized action on FSH-dependent differentiation.

Animals↗
PubMed1987

Adhesion and differentiation of cultured rat granulosa cells: role of fibronectin.

Because fibronectin is a major secretion product of rat granulosa cells in culture, we have investigated 1) the involvement of endogenous fibronectin in granulosa cell attachment, and 2) the consequences of inhibition of this attachment on follicle-stimulating hormone (FSH)-dependent differentiated responses. Attachment was significantly inhibited for up to 8 h in a concentration-dependent manner by antiserum to rat fibronectin, but not by nonimmune serum. Adsorption of antiserum on fibronectin or addition of exogenous fibronectin eliminated this inhibitory activity. Treatment with antiserum did not significantly alter the FSH-dependent production of adenosine 3',5'-cyclic monophosphate over 2 h or progestins over 48 h, while conversion of testosterone to 17 beta-estradiol over 48 h was suppressed by 60% in the presence of antiserum, regardless of antiserum adsorption on fibronectin. Results indicate that endogenous fibronectin is involved in substratum attachment of rat granulosa cells, but that attachment is not a requisite for FSH responsiveness.

Animals↗
PubMed1987

Ganglioside inhibition of attachment and differentiation of cultured rat granulosa cells: interactions with fibronectin.

The involvement of fibronectin in the attachment and differentiation of rat granulosa cells, cultured in a chemically defined medium, was investigated using the inhibitory properties of mixed brain gangliosides (MBGs) and highly purified disialoganglioside, GD1a. MBGs inhibited cell attachment to plastic culture surfaces in a concentration-dependent manner, with 0.1 mmol l-1 causing significantly decreased attachment between 0.5 and 24 h of incubation. Inhibition of attachment to a fibronectin-coated substratum was even greater. The inhibitory effect of MBGs was not caused by binding to the cell surface, but instead the inhibitory factor(s) were adsorbed on a surface of immobilized human plasma fibronectin, thereby preventing cell attachment to this surface. The inhibitory action of MBGs was also neutralized by the addition of soluble fibronectin. Furthermore, at least one component of MBGs, detected chemically following thin-layer chromatography, was directly shown to bind to human fibronectin. MBGs inhibited to varying degrees the follicle-stimulating hormone(FSH)-dependent responses: augmentation of cellular protein content, production of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and progestins (progesterone + 20 alpha-hydroxypregn-4-en-3-one + pregnenolone), and induction of aromatase activity. These inhibitory activities of MBGs could not be eliminated by adsorption on immobilized fibronectin or reversed by addition of soluble fibronectin, thus distinguishing these actions from the early inhibition of cell attachment. FSH-dependent responses were also inhibited by GD1a, while responses to stimulation by dibutyryl cyclic AMP plus 3-isobutyl-1-methyl xanthine were less affected by this ganglioside. These results suggest that gangliosides inhibit attachment of granulosa cells in culture by binding to fibronectin, whereas the inhibition of FSH-dependent differentiation occurs by other modes of action that are unrelated to the effects on cell adhesion.

Animals↗
PubMed1986

Biliary tract dilatation in acquired immune deficiency syndrome.

Biliary tract dilatation without obstruction may result from sclerosing cholangitis, pyogenic cholangitis, or bile duct surgery. This case report describes a patient with AIDS whose biliary tract dilatation was due to cytomegalovirus infection. Such a diagnosis should now be considered in the immuno-suppressed patient who has dilated bile ducts.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The late effect of grenade fragments.

Following the explosion of a grenade or shell, the victim may be peppered with literally hundreds of pieces of metal. Troublesome fragments which perforate a major viscus may be removed but others are often left behind, as it is felt (usually correctly) that these fragments will cause no harm. We describe a case in which a grenade fragment received 16 years previously pierced the large bowel. A psoas abscess developed which was located by ultrasound. Pus was aspirated under ultrasound control and the lesion was successfully treated by antibiotics.

Abscess↗
PubMed1983

Early detection of obstructed ureter by ultrasound following renal transplantation.

Serial ultrasound examinations were carried out following 144 renal transplants. Eleven patients (8%) required surgery for ureteric obstruction and in all cases the ultrasound correctly identified the obstruction at an early stage. One false positive result was obtained with the ultrasound and this compared favourably with both the intravenous urogram (IVU) and isotope renogram. There were false positive and false negative results with both the IVU and renogram in addition to which neither of these techniques, particularly the IVU, is as simple or atraumatic for the patient as the ultrasound. Serial ultrasound examinations have a useful role in the detection of ureteric obstruction as well as being of value in the detection of perinephric fluid collections and acute rejection.

Diagnostic Errors↗
PubMed1982

Ultrasonic characterisation of diffuse liver disease - the relative importance of frequency content in the A-scan signal.

Successful methods of ultrasonic characterisation of alcohol-induced diffuse liver disease using texture analysis (Lerski et al. 1979, 1980a, b) have studied the radiofrequency (RF) A-scan ultrasonic signal. In the present paper the Fourier spectra of such signals have been partitioned and a statistical analysis implemented to determine the diagnostic usefulness of certain frequency groups present in the signal. Although this method has not, of itself, been found to compared favourably with texture analysis it has shown that useful information is present in the high frequency portion of the frequency spectra. This information would not be available if the smoothed and denodulated A-scan signal were studied.

Fatty Liver, Alcoholic↗
PubMed1982

Abnormal aortic valve echoes in mitral prolapse. Echocardiographic features of floppy aortic valve.

The following distinctive combination of M-mode and two dimensional echocardiographic abnormalities of the aortic valve was observed in a group of 12 patients, of whom 11 had mitral valve prolapse. On two dimensional scans, the aortic cusps were freely mobile but appeared thickened or folded. On M-mode records, cusp excursion was normal: there was well defined systolic oscillation, and cusp echoes were multiple and centrally positioned within the aortic root during diastole. The aortic valve was inspected at operation in two patients: a typically myxomatous valve was replaced in one and findings were in keeping with this diagnosis in the other. It is suggested that the echocardiographic features described are characteristic of the floppy aortic valve. Despite the echocardiographic abnormalities, only three patients had clinical evidence of an aortic valve lesion. It is, therefore, further suggested that the investigation of patients with mitral prolapse should include echocardiographic assessment of the aortic valve, even when associated myxomatous degeneration of that valve is not suspected clinically.

Adolescent↗