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Biomedical subjects

A Lynch

Publications and source records attributed to A Lynch.

At least 73 records · Page 4Linked to original sources

Pulsatile progesterone secretion: its relevance to clinical evaluation of corpus luteum function.

Pulsatile progesterone (P) secretory patterns were characterized in rhesus macaques (n = 13) during the midluteal phase (cycle days 18 to 20) of the normal ovarian/menstrual cycle. Sixty high-amplitude (greater than 1 ng/ml) P pulses were observed during a total of 169 hours of sampling. Typically, P pulses had an ultradian periodicity of 2 hours and were independent of detectable luteinizing hormone (LH) and prolactin (PRL) pulses in 70% of instances. LH pulses were associated with a concomitant P and PRL pulse in 100% to 80% of occasions, respectively. Pulsatile P release was augmented by exogenous cynomolgus monkey LH and suppressed by administration of a gonadotropin-releasing hormone antagonist. Two individuals with apparently normal ovulation and once daily plasma P concentrations within the normal range demonstrated a nonpulsatile P profile. These findings encourage clinical investigations to characterize pulsatile P secretion in normal women and patients in whom corpus luteum dysfunction is suspected.

Animals↗

Selective inhibition of follicle-stimulating hormone by porcine follicular fluid extracts in the monkey: effects on midcycle surges and pulsatile secretion.

Nonsteroidal factor(s) in porcine follicular fluid (pFF) can selectively suppress tonic follicle-stimulating hormone (FSH) concentrations when administered in the follicular phase to monkeys. Here it is demonstrated that when administered in either the early follicular phase or in the midst of the spontaneous preovulatory estradiol (E2) surge (E2 greater than or equal to 200 pg/ml), pFF preferentially inhibits FSH or blocks the FSH surge, respectively, whereas immunoassayable and bioassayable luteinizing hormone (LH) surges persist. Delay in the timing of ovulation uniformly follows follicular phase pFF administration, and corpus luteal insufficiency is often seen. The inhibitions of FSH in circulation were achieved by a decrease in amplitude and frequency of FSH pulses. No discernible effect on LH pulsatility was observed.

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Maintenance of ovulatory menstrual cycles in chronically cannulated monkeys: a vest and mobile tether assembly.

We report maintenance of apparently normal ovulatory menstrual cycles in cynomolgus monkeys up to 3 months after their placement in a vest and mobile tether assembly, with or without chronic cannulation via a femoral to vena caval catheter. Since menstrual cyclicity and characteristic hormonal profiles of the principal ovarian steroids remained normal in these monkeys, use of the vest and mobile tether apparatus described here permits long-term study of the hypothalamic-pituitary-ovarian axis during chronic cannulation without introducing overt aberrancies as a part of the experimental model.

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Hyperprolactinemia in monkeys: induction by an estrogen-progesterone synergy.

To evaluate the synergistic effect of estrogens and progesterone on prolactin secretion, rhesus and cynomolgus monkeys in the early follicular phase received estradiol benzoate (100 microgram/kg/day, sc) alone for 14 days, then in combination with progesterone (subcutaneous silastic capsule) for an additional 14 days. Blood was drawn daily by femoral venipuncture under ketamine hydrochloride anesthesia (15 mg/kg). Similarly, this protocol for exogenous steroid treatment was employed in a monkey having a chronically indwelling (femoral insertion into the vena cava) cannula maintained by a vest and mobile tether apparatus; however, no anesthesia was used to obtain serum specimens. In addition, this assembly was applied to six monkeys to determine the acute effects of ketamine hydrochloride on prolactin secretion. Concentrations of prolactin, estradiol-17 beta, and progesterone in serum were determined by conventional radioimmunoassays. Under estrogen therapy alone, mean circulating prolactin levels declined from approximately 15 to less than 5 ng/ml; in contrast, the addition of progesterone caused an abrupt serum prolactin elevation, approximately 8-12 fold. This estradiol-progesterone course led to sustained hyperprolactinemia in the chronically catheterized monkey, whereas ketamine administration raised serum prolactin only briefly, the elevation lasting less than three hours after injection. These findings establish that an estrogen-progesterone synergy, separate from the transient effects of ketamine, induced hyperprolactinemia in cycling monkeys having prevailing levels of estrogen and progesterone near those characteristic of late gestation, when sustained prolactin elevations are observed normally.

Animals↗

Pulsatile pituitary gonadotropin secretion during maturation of the dominant follicle in monkeys: estrogen positive feedback enhances the biological activity of LH.

In the follicular phase of the menstrual cycle, pulsatile patterns of LH and FSH secretion in monkeys change during maturation of the dominant follicle. At the preovulatory surge, the most striking event is the prodigious elevations of bioassayable LH, rising up to 50-fold within 24 h. Principally, establishment of the surge is due to marked enhancement of the amplitude of LH secretory pulses. In contrast, LH and FSH measured by RIA enter, in parallel, the surge modes of secretion approximately 5 h later than bioassayable LH and rise more slowly; the B:I ratio may reach 10:1. This same disparity between bioassayable versus immunoassayable LH was induced in castrate monkeys under estrogen positive feedback stimulation. We conclude that the preovulatory estrogen surge promotes the secretion of an LH molecule(s) having enhanced biological activity.

Animals↗

Control of rat skeletal-muscle phosphorylase phosphatase activity by adrenaline.

Administration of adrenaline to an isolated rat hindlimb preparation rapidly decreased muscle phosphorylase phosphatase (EC 3.1.3.17) activity and increased heat-stable and trypsin-labile phosphatase inhibitor activity. This was associated with increased tissue cyclic AMP concentrations, phosphorylase (EC 2.4.1.1) activation and glycogen synthase (EC 2.4.1.11) inactivation.

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Prenatal progesterone. I. Its effect on development and on intellectual and academic achievement.

The development of two groups of children whose mothers had been given progesterone supplements during pregnancy to relieve symptoms of toxaemia was assessed, one group at 2 yr of age and the other at 16 yr of age. There was no evidence that progesterone supplements accelerated development in the 2-yr-old age group or enhanced intellectual and academic attainment in the 16-yr-old age group. In addition, the evidence regarding the reported beneficial effects on intellectual attainment of in utero exposure to excess sex steroids is discussed.

Achievement↗

Prenatal progesterone II. Its role in the treatment of pre-eclamptic toxaemia and its effect on the off-spring's intelligence: a reappraisal.

Dalton's results concerning the beneficial effect of progesterone supplementation in preventing pre-eclamptic toxaemia [16] and in enhancing intellectual potential [17,18] were reappraised. We could find no evidence in the data that progesterone supplementation was any better at preventing pre-eclamptic toxaemia than treating the disorder symptomatically. Nor could we find any convincing evidence that excess progesterone enhances development at 1 yr of age, academic attainment at 9--10 yr of age, or success in school leaving examinations and improves the chances of continuing further full-time education after leaving school.

Achievement↗

Postnatal undernutrition: an alternative method.

Rat pups were undernourished from birth by placing them for 12 hr/day with a normal lactating mother and 12 hr/day with a nipple-ligated mother each day for 25 days. The method resulted in a marked delay in the body growth of the undernourished pups, especially during the first 2 weeks of life. Observations of the behavior of the mothers towards the underfed pups were made at different times of the day and compared to the behavior of the mothers suckling well-fed pups. The results show that (1) nipple-ligated mothers are able to provide adequate maternal care for undernourished pups, and (2) both ligated and nonligated mothers caring for underfed pups spend more time with those pups than mothers caring for well-fed pups.

Age Factors↗

Regulation of rat liver glycogen synthesis and activities of glycogen cycle enzymes by glucose and galactose.

Direct regulation of rat liver glycogen metabolism by glucose and galactose was studied using an isolated liver perfusion system. Activation of glycogen synthase and net glycogen synthesis increased linearly when perfusate glucose concentration was increased from 125 to 500 mg/100 ml. Galactose, rapidly taken up by isolated rat liver regardless of circulating glucose concentration, increased these responses to glucose. In the presence of galactose (greater than or equal to 5 mg/100 ml), activation of synthase and glycogen synthesis were 1.5-fold higher at any given glucose concentration. The addition of insulin did not appreciably after synthase activation by glucose and galactose. Phosphorylase activity, low at circulating glucose levels above 125 mg/100 ml, was further decreased as glucose was increased or when galactose was added to the perfusate. Release of glucose into the perfusate in response to aglycemia was increased in the presence of galactose.

Animals↗

Glycogen regulation in isolated perfused near term monkey liver.

Glycogen metabolism was studied in the isolated perfused liver of the monkey conceptus at 90% of gestation using an in situ recirculating perfusion system. Net uptake of glucose and galactose and the activities of the enzymes, glycogen synthetase and phosphorylase, were studied in response to varied perfusate composition. Synthetase activity was expressed as %I. the percentage of total synthetase activity in the active form. Perfusate glucose concentrations as high as 700 mg/100 ml did not lead to net glucose uptake of to an increase in the baseline %I synthetase (4 +/- 1, mean +/- SEM). In the presence of 300 mg/100 ml glucose, insulin at 10(-7) M in creased %I to 8 +/- 2, and galactose greater than 75 mg/100 ml increased %I to 8 +/- 1. The combination of galactose, glucose, and insulin increased %I to 40 +/- 5. With this latter combination, synthetase activity was proportional to perfusate glucose concentration above 100 mg/100 ml. Phosphorylase activity was diminished by either galactose or insulin, and phosphorylase activity was lowest in the group receiving galactose, glucose, and insulin. Galactose was taken up by all livers, but net glucose uptake was not observed under any condition; net hexose uptake was observed in perfusions with galactose. Glycogen levels did not vary significantly with varied perfusate composition during the 30-min perfusion periods.

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Motor co-ordination and cerebellar size in adult rats undernourished in early life.

The male progeny of mother rats which had been undernourished during most of gestation and all of lactation were divided into two groups when weaned at 25 days. One group was nutritionally rehabilitated (G-L-) while the other was underfed for a further 9 weeks (G-L-W-) before nutritional rehabilitation. Despite this further undernutrition the G-L-W- rats eventually caught up in both body and brain weight with the G-L- group. Compared with control rats of the same age that had been well fed throughout life, the G-L- and G-L-W- animals had permanent deficits in body and regional brain weights. At 36 weeks rats were given two tests of motor co-ordination. They were required (a) to run backwards on a revolving drum and (b) to cross a chasm bridged by a ladder or parallel rods for a food reward. Both previously undernourished groups did consistently worse than controls of the same age or of similar body weight on two measures of co-ordination: falls from the revolving drum and stumbles on the bridge-crossing test. It is postulated that these differences indicate impaired cerebellar function in the prevously undernourished rats.

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