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Biomedical subjects

R F Seamark

Publications and source records attributed to R F Seamark.

At least 91 records · Page 5Linked to original sources

Concentrations of steroid hormones, and of prolactin, in washings of the human uterus during the menstrual cycle.

Levels of steroid hormones, prolactin and protein were determined in trans-cervical flushings of uteri of 73 consenting women presenting for reversal of sterilization. Median total levels of steroids (pmol), prolactin (mu i.u.) and protein (mg) in the washings were: pregnenolone, 4.22; pregnenolone sulphate, 15.1; progesterone, 1.01; dehydroepiandrosterone (DHEA), 8.92; DHEA sulphate, 368; androstenedione, 2.23; testosterone, 1.04; oestrone, less than 0.7; oestrone sulphate, 0.49; oestradiol, 0.08; prolactin, 23.8; and protein, 5.75. Levels of these components of uterine flushings did not vary significantly between Days 6-10, 11-14, 15-20 and 21-28 after the onset of the previous menstrual period (P greater than 0.05). Uniform levels of free steroids in uterine washings throughout the menstrual cycle, and low free steroid/total protein ratios (all less than 3 pmol/mg), support other evidence for a paucity of steroid-binding proteins in human histotroph. The predominance of DHEA sulphate and of pregnenolone sulphate in human uterine washings is in accord with their abundance in plasma, and may provide an important precursor pool for de-novo steroidogenesis by human embryos before implantation. Our results support the view that human histotroph is a filtrate of plasma.

Dehydroepiandrosterone↗

Angiotensin I and II in the assessment of baroreceptor function in fetal and neonatal sheep.

In fetal and neonatal sheep intravenous injections of angiotensin I, angiotensin II and noradrenaline each increased mean blood pressure and decreased heart rate in a dose-dependent manner. Blood pressure responses to given doses of angiotensin I and II were larger in neonatal than fetal animals while the reverse was true for noradrenaline. In both sheep groups angiotensin II was more pressor than angiotensin I. Baroreceptor function was assessed by correlating blood pressure response to angiotensin II with corresponding changes in either heart rate or heart period. A more sensitive baroreceptor reflex was found in the fetal group in that a given blood pressure response resulted in a significantly larger bradycardia and the calculated gain of the reflex was higher. In those fetuses subjected to either bilateral vagotomy or cervical cord transection pressor responses to both angiotensin II and noradrenaline were enhanced but a significant change was only seen in the cervical cord transection fetuses. Heart rate responses to these drugs were essentially unchanged in the cervical cord transected fetuses while in vagotomized fetuses the bradycardia with each drug was replaced by a tachycardia. It is concluded that the baroreflex is more active in the fetus than the neonate and is mediated by autonomic effector mechanisms similar to those found in the adult.

Angiotensin I↗

Deuterium labelled steroid hormones: tracers for the measurement of androgen plasma clearance rates in women.

A method employing stable isotope-labelled tracers and gas chromatograph-mass spectrometry (GC-MS) analysis has been used to measure the plasma clearance rates (PCR's) of androstenedione (A) and testosterone (T) in normal women and women with androgen abnormalities including hirsutism and polycystic ovary syndrome. A solution of deuterium-labelled A and T is infused at a constant rate and blood samples taken at 2 and 2.25 h. Solvent extracts of the derived plasma samples, to which an internal standard has been added, are derivatized with pentafluoropropionic anhydride and the endogenous steroid and deuterated steroid are quantitated after an injection of the derivatization mixture into a capillary column GC-MS. The concentration of the deuterated steroid in the infusion mixture is measured and the PCR is calculated. In premenopausal normal women the PCRA is 1950 +/- 184 1/24 h (n = 5) and the PCRT is 484 +/- 82 1/24 h (n = 7).

Androgens↗

Serum melatonin profiles and endocrine responses of ewes exposed to a pulse of light late in the dark phase.

To determine whether effects of light pulses on the photoperiodic time measuring system involve changes in pineal gland function, melatonin profiles were determined in groups of ewes maintained under 10-h light, 14-h dark (10L:14D) or 10L:10D:1L:3D. Ewes exposed to 10L:14D had a significantly (P less than 0.01) longer duration of melatonin secretion (15.0 +/- 0.4 h, mean +/- SE) than ewes under 10L:10D:1L:3D (9.0 +/- 0.4 h). The 1-h pulse of light therefore acted as a dawn signal in the latter group. During a period of extended darkness imposed to study endogenous control of melatonin release, there was no change in the duration of elevated melatonin in control ewes (16.1 +/- 0.5 h), but a significant (P less than 0.05) lengthening occurred in pulsed ewes (13.2 +/- 1.4 h). PRL responses to a bolus iv injection of TRH (50 ng/kg BW) were significantly (P less than 0.01) smaller in control ewes (478 +/- 134 ng/ml) compared with pulsed ewes (1578 +/- 175 ng/ml), with responses in the latter group resembling those observed in ewes on long days. A 1-h pulse of light late in the dark phase, therefore, resulted in a melatonin pattern normally observed under long days in ewes, and this was associated with other endocrine functions also characteristic of sheep on long days. It is concluded that pulses of light modify activity of the pineal gland which in turn interacts with the photoperiodic time-measuring system via melatonin. The increase in duration of melatonin secretion observed in pulsed ewes under extended darkness suggests that the melatonin rhythm is under the control of two oscillators coupled to dusk and dawn, and that these oscillators interact more strongly when compressed by an interrupted dark phase.

Animals↗

The relation between calcium absorption, serum dehydroepiandrosterone, and vertebral mineral density in postmenopausal women.

Vertebral mineral density, measured by computerized axial tomography, radiocalcium absorption, serum dehydroepiandrosterone (DHA), and serum cortisol (C) were measured in 98 postmenopausal women aged 56-70 yr. On the basis of spine radiographs and fracture history, the women were classified into 49 normal subjects (mean age, 60.5 yr) and 49 with osteoporosis (mean age, 63.1 yr). Vertebral mineral density (VMD), radiocalcium absorption (alpha), serum DHA, and the ratio of DHA to cortisol (DHA/C) were all significantly lower in the osteoporotic than in the normal subjects. DHA was significantly related to C in both groups but the regression was significantly flatter in the osteoporotic than in the normal subjects. Calcium absorption did not fall significantly with age in either group. In the normal group VMD, DHA, and DHA/C fell with age but VMD was not related to alpha, DHA, or DHA/C. In the osteoporotic group, VMD did not fall significantly with age but was significantly related to alpha and DHA/C. Stepwise regression analysis showed that in the normal subjects, age was the only variable significantly related to VMD (P less than 0.05). In the osteoporotic group, calcium absorption was the main determinant of VMD, with age and DHA/C contributing much less to the variance. Discriminant function analysis showed a theoretical misclassification of 45% of cases using DHA, 39% using DHA/C, 32% using alpha, and 18% when alpha and DHA or DHA/C were both taken into account. It is concluded that malabsorption of calcium is a significant risk factor for postmenopausal osteoporosis, probably because of a secondary increase in bone resorption to maintain serum calcium. The severity of the osteoporosis is directly related to the severity of the calcium malabsorption. Low serum DHA appears to represent a further risk factor, either because of its role as estrogen precursor or (possibly) because it promotes bone formation. However, the severity of the osteoporosis was not related to the serum DHA level and only weakly to the DHA/C ratio.

Aged↗

Steroid hormones in uterine washings and in plasma of gilts between days 9 and 15 after oestrus and between days 9 and 15 after coitus.

Between Days 9 and 15 after oestrus, concentrations of pregnenolone, pregnenolone sulphate, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, oestrone and oestrone sulphate in free uterine fluid collected from non-pregnant gilts were greater than respective values in plasma (P less than 0.05). The total contents of pregnenolone, progesterone, DHEA, testosterone, oestrone and oestradiol in washings from pregnant uteri exceeded (P less than 0.05) respective non-pregnancy levels during this same period. Concentrations of pregnenolone, pregnenolone sulphate, DHEA, DHEA sulphate, androstenedione, oestrone, oestrone sulphate and oestradiol in free uterine fluid recovered from gravid uteri were also higher (P less than 0.05) than respective plasma values. By contrast, the progesterone concentration in uterine fluid from pregnant animals was lower (P less than 0.001) than the plasma value. Concentrations of DHEA, DHEA sulphate, androstenedione and oestrone sulphate in plasma of pregnant gilts between Days 9 and 15 after mating exceeded (P less than 0.05) the respective concentrations in unmated gilts between Days 9 and 15 after oestrus. Plasma levels of pregnenolone sulphate were lower (P less than 0.05) in the pregnant animals. We therefore suggest that the endometrium of the pig can concentrate steroid hormones in uterine fluid and that increases in steroid levels in this milieu between Days 9 and 15 after coitus reflect steroidogenesis by embryonic tissues and modification of enzyme activities within uterine tissues under the influence of progestagens. The pool of steroid sulphoconjugates present in uterine fluid between Days 9 and 15 post coitum could serve as an important precursor source for progestagen, androgen and oestrogen synthesis by tissues of pig embryos before implantation.

Androstenedione↗

On the origin of dehydroepiandrosterone sulphate in the blood of fetal sheep.

Total sulphoconjugated and unconjugated dehydroepiandrosterone (DHA) and total oestrone were measured in plasma of intact sheep fetuses, fetuses hypophysectomized at 104-112 days and fetuses bilaterally adrenalectomized at 98-101 days. At 120-127 days, the mean concentrations of total DHA and oestrone in intact fetuses (n = 13) were 29.7 +/- 4.2 (S.E.M.) nmol/l and 14.3 +/- 2.8 nmol/l respectively. At term, the values for total DHA and oestrone in hypophysectomized fetuses (n = 13) of 18.0 +/- 1.9 nmol/l and 9.1 +/- 2.0 nmol/l were significantly (P less than 0.05) lower than the intact group whereas in the adrenalectomized fetuses (n = 8) total DHA (80.8 +/- 13.0 nmol/l) was higher (P less than 0.05) and total oestrone values were similar to the intact animals. Intrafetal infusion of cortisol at term (1 mg/h for 84 h) raised levels of total oestrone in intact (n = 6; 12.3 +/- 2.9 vs 31.6 +/- 8.5 nmol/l) and adrenalectomized (n = 4; 14.2 +/- 2.6 vs 190.6 +/- 53.0 nmol/l) fetuses and of total DHA in hypophysectomized fetuses (n = 7; 16.0 +/- 1.9 vs 31.6 +/- 8.5 nmol/l) while infusion of ACTH (1-24) (5 micrograms/h) was without significant effect in any group. It is concluded that the ovine fetal adrenal in late pregnancy makes no significant contribution either to the high circulating concentrations of DHA sulphate or to the substrates for placental oestrogen synthesis.

Adrenal Glands↗

Oral contraceptives, pregnancy, and endogenous oestrogen in gall stone disease--a case-control study.

A case-control study of gall stone disease in women in relation to use of contraceptives, reproductive history, and concentrations of endogenous hormones was undertaken. The study population comprised 200 hospital patients with newly diagnosed gall stone disease, 182 individually matched controls selected from the community, and 234 controls who were patients in hospital. Use of oral contraceptives was associated with an increased risk of developing gall stones among young subjects but a decreased risk among older subjects. The risk of developing gall stone disease increased in association with increasing parity, particularly among younger women. The risk fell with increasing age at first pregnancy, independent of parity. Mean urinary excretion over 24 hours of oestrone, but not of pregnanediol, was significantly (p less than 0.05) greater for postmenopausal patients than controls. The age dependence of the relative risk associated with exposure to oral contraceptives and pregnancy suggests that there are subpopulations of women susceptible to early formation of gall stones after exposure to either oral contraceptives or pregnancy.

Adult↗

N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesis.

Although the hypothesis that melatonin may act by inhibiting prostaglandin synthesis arose in part from the similar structures of melatonin and indomethacin, melatonin does not share the in vitro efficacy of indomethacin in inhibiting prostaglandin synthesis. One possibility is that a metabolite of melatonin formed within the target cell might inhibit prostaglandin synthesis and in this study we have tested this by examining the action of the two oxidised metabolites, N-formyl-N-acetyl-5-methoxy kynurenamine formed by the action of indole 2,3-dioxygenase and N-acetyl-5-methoxy kynurenamine , formed in the brain by the action of formamidase . This latter compound which has a structure resembling the fenamate inhibitors of PG biosynthesis had a marked and time dependant inhibiting effect in synthesis using bovine and ovine seminal vesicle microsome preparations and measuring the products by using (1-14C) arachidonic acid and by using a specific antiserum for PGE methyl oxime.

Animals↗

In vitro fertilization and embryo transfer program, Department of Obstetrics and Gynecology, University of Adelaide at the Queen Elizabeth Hospital, Woodville, South Australia.

A review is presented summarizing the in vitro fertilization experience at the University of Adelaide, Australia. Initial attempts utilizing the normal cycle were unsuccessful in obtaining a pregnancy. Since 1982 the overall ongoing pregnancy rate has been 21% per embryo transfer, 16% per laparoscopy, and 12% per treatment cycle. A detailed description of presently utilized methodology is presented.

Adult↗

Effects of pinealectomy, oestradiol and melatonin on plasma prolactin and LH secretion in ovariectomized sheep.

The study examines whether the pineal gland mediates in the seasonal rhythm in the response of the hypothalamo-pituitary axis to oestrogen in the sheep. Five groups of ewes, each comprised of five sham-pinealectomized ewes and five pinealectomized ewes, were maintained under field conditions over a 2-year period. Group I ewes were ovariectomized and treated with two oestradiol capsules in the first year and one oestradiol capsule in the second year; group 2 ewes were ovariectomized and treated with two oestradiol capsules and three melatonin sachets in the first year and one oestradiol capsule and three melatonin sachets in the second year; group 3 ewes were ovariectomized and treated with three melatonin sachets in the first year and one oestradiol capsule in the second year; group 4 ewes were ovariectomized and treated with empty implants; group 5 had intact ovaries. Blood samples were taken at weekly intervals for determination of plasma prolactin, LH and FSH levels. Cyclic ovarian activity, determined by rams fitted with a marking harness, occurred in both sham-pinealectomized and pinealectomized ewes in group 5 during December to May in both years. A circannual rhythm in plasma prolactin levels was apparent in all ten groups of animals. The levels were highest in spring (September to November) and decreased before the onset of breeding activity in midsummer (December). Ovariectomized ewes with intact pineal glands and treated with oestradiol capsules (group 1) exhibited marked changes in LH and FSH concentrations during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Incidence of multiple pregnancy after in-vitro fertilisation and embryo transfer.

7 multiple pregnancies occurred in a series of 20 pregnancies after oocyte recovery for in-vitro fertilisation and embryo transfer. After ovarian stimulation with clomiphene alone or with human menopausal gonadotropin, 102 laparoscopies were carried out in 62 women and the ongoing pregnancy rate beyond the first trimester was 17/102 laparoscopies (17%), including 5 sets of twins. 1 triplet and 1 twin pregnancy showed evidence of regression of two sacs and one sac, and both are progressing as singleton pregnancies at 16 and 34 weeks, respectively. 3 abortions occurred at 7, 8, and 9 weeks--a spontaneous abortion rate of 15%. The pregnancy and multiple pregnancy rates after stimulation with clomiphene alone or with human menopausal gonadotropin were comparable, but oocyte pickup based on a knowledge of the duration of the endogenous rise in luteinising hormone, rather than 36 h after administration of human chorionic gonadotropin, increased the pregnancy rate. As the quality and number of embryos transferred to the uterus increased, the risk of multiple pregnancy also rose. Consideration should therefore be given to restricting the number of embryos transferred to limit multiple pregnancies to twins.

Adult↗

Inhibition of gastric acid secretion in the gastric brooding frog, Rheobatrachus silus.

The female gastric brooding frog Rheobatrachus silus broods its young in its stomach. A substance that inhibits gastric acid secretion in a toad stomach preparation in vitro appears to be secreted by the developing young. This substance has been identified as prostaglandin E2. Rheobatrachus silus may thus have developed a mechanism whereby prostaglandin secreted by the larvae inhibits acid secretion in the stomach of the female until the larvae have completed development and emerged as juvenile frogs by way of the female's mouth.

Animals↗

Neonatal water metabolism: an objective postnatal index of intrauterine fetal growth.

The water metabolism of 103 newborn babies was determined over the first 10 postnatal days, by measuring water turnover rates by means of an isotope dilution technique. This technique involves the oral administration of the non-radioactive isotope of water, 2H2O, and the measurement of its urinary excretion by infrared spectrophotometry. The slope of the excretion curve after equilibration with the infant's body water was mathematically expressed as the rate constant. Using multiple obstetric and paediatric criteria, the babies were clinically classified into one of three categories, fully grown ("normal'), borderline or clearly growth retarded. The median values of the rate constants X 10(4) (h-1) for the three groups were 73.3, 85.9 and 100.2 and were highly significantly different from each other (P less than 0.0005) with no overlap of the 97% non-parametric confidence limits of each group. Neonatal water turnover increased with the clinical degree of intrauterine fetal growth retardation and within the limits of this study, this finding was unaffected by gestational age, birth weight or the neonatal environment. The results suggest that neonatal water metabolism is an objective postnatal index of fetal growth retardation.

Body Water↗

Special uses of a gas chromatograph-mass spectrometer in endocrinology.

Based on the isotope dilution principle, and using deuterium-labelled steroids as tracers combined with GC-MS analysis, clinically acceptable procedures for the measurement of daily urinary production rates (UPR's) and metabolic clearance rates (MCR's), of hormonal steroids, have been developed. In clinical tests, using progesterone and androstenedione as models the UPR's and MCR's obtained compared favourably with values obtained using radioisotope-labelled tracers. The heavy isotope procedure proved, however, to be superior to the radioisotope methods in accuracy, speed and patient safety.

Androstenedione↗

Applications of heavy isotope tracers to clinical studies: progesterone urinary production rate determination in the menstrual cycle and pregnancy.

A method for the in vivo determination of progesterone production rate using progesterone labeled with deuterium as the tracer and gas chromatography-mass spectrometry for assessing isotope dilution in a urinary metabolite is described. By measuring the ratio of labeled to unlabeled free progesterone in a 24-h urine sample, the problem of identifying a unique metabolite appears to have been avoided. Median progesterone production rates on day 7 of the follicular phase and day 7 of the luteal phase were 3.5 mumol/24 h and 72.6 mumol/24 h, respectively. Where repeated determinations were performed through the luteal phase in two nonconceptual cycles, the familiar midluteal plateau of progesterone production was noted. The MCR of progesterone calculated from luteal phase data was 2051 1/24 h (SD, 275 1/24 h). When determined in pregnancy, progesterone production varied from 250 mumol/24 h at 6 weeks in a singleton pregnancy, to 1565 mumol/24 h at 35 weeks in a triplet pregnancy. Repeated determinations before term in a twin pregnancy detected no evidence of decreasing progesterone production before labor. The value of urinary pregnanediol and plasma progesterone to indirectly monitor progesterone production were confirmed.

Adult↗