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Biomedical subjects

C A Nagle

Publications and source records attributed to C A Nagle.

At least 19 recordsLinked to original sources

Effects of a copper-bearing intrauterine device on the ovarian function, body weight gain and pregnancy rate of nulliparous heifers.

A copper-bearing intrauterine device (IUD), designed to cause a slight distention of the uterus, was inserted through the cervix into each uterine horn of 230 heifers; an additional 230 heifers served as the control group. Blood was drawn at 0, 1, 2, 20 and 120 d for progesterone and testosterone assays. The heifers were checked twice daily for estrus and examined at 0, 60 and 120 d for weight gain. Thereafter they were bred over a 120-d period. The IUD caused anestrus in 98% of the heifers, with a daily weight gain 25.5 % higher than in the control heifers. Moreover, the device was 100% effective in preventing pregnancy. At 20 and 120 d after IUD insertion progesterone levels averaged 0.7 ng/ml, which was 4 to 5 times lower than in the control animals, suggesting a failure in ovulation or in corpus luteum (CL) formation due to the IUD. Simultaneously, testosterone values were increased up to 8 times in IUD-treated heifers, reaching a mean concentration of 163 pg/ml. Associated histological evaluations of the ovaries from UD-treated heifers revealed the presence of 2 or more cysts per ovary, with marked hyperthecosis in many antral follicles in which the granulosa cell layers were either thinned or lacking. The results suggest that the action of the copper-releasing IUD used in this study resulted in high contraceptive efficiency but also in disturbance of ovarian function. Our findings further raise the possibility of a cause and effect relationship between hyperandrogenism and the higher body weight gain observed in heifers treated with the IUD.

Journal Article↗

Morphometric study of the testicular interstitial tissue of the monkey Cebus apella during postnatal development.

The purpose of this study was to evaluate the developmental changes of the Leydig cells and their precursors during postnatal development in the monkey Cebus apella. Four groups of monkeys were studied: neonatal, infantile, early pubertal and late pubertal. Light microscopy, immunocytochemistry, electron microscopy and stereological studies were performed to determine cytologic and cytochemical characteristics, volume density, absolute volume and cell counts of Leydig cells. In the interstitial tissue two components were recognized: specific interstitium comprising mature and immature Leydig cells and differentiating Leydig cell precursors, and non-specific interstitium including connective tissue and blood vessels. Mature Leydig cells were polygonal with a round, euchromatic nucleus and abundant cytoplasm. Immature Leydig cells were more elongated and the nucleus showed more heterochromatin. Mature and immature Leydig cells showed either a pale- or a dark-stained cytoplasm. Pale Leydig cells showed abundant smooth endoplasmic reticulum (SER), mitochondria with tubular cristae and glycogen granules. The SER of dark Leydig cells consisted of abundant flat cisternae, only few glycogen inclusions and abundant lipid droplets. All Leydig cells were intensely reactive for 3beta-hydrohysteroid dehydrogenase (3beta-HSD). Some peritubular cells acquired nuclear and cytoplasmic characteristics that indicated that they were differentiating to Leydig cells, as evidenced by the strong 3beta-HSD positivity found in scattered elongated cells of the peritubular tissue. Absolute interstitial volume increased from birth to the end of puberty due to an increment in Leydig cells numbers and size. The mature and immature Leydig cell populations showed a different evolution during postnatal development. While immature Leydig cells increased 7-fold from the neonatal to the early pubertal period and increased at a lower rate during puberty, mature Leydig cells remained stable until early puberty and increased significantly during late pubertal development.

Animals↗

Is infancy a quiescent period of testicular development? Histological, morphometric, and functional study of the seminiferous tubules of the cebus monkey from birth to the end of puberty.

The objective of this study was to describe the maturational changes observed in the seminiferous tubules of the monkey Cebus apella, a New World primate species, from birth to the end of puberty. Nineteen animals were subdivided into four groups: neonatal (1-40 days), infantile (4 months to 1 yr), early pubertal (1 yr, 8 months to 2 yr, 9 months), and late pubertal (4-8 yr). Volumetric determinations of different testicular components were made, tubule diameter and length were calculated, and spermatogenic cells, Sertoli cells, and androgen-binding protein secretion were quantified. Testicular and seminiferous tubule volumes increased significantly in the first 5 months of life and during puberty due to the combined increment in seminiferous tubule diameter and length. The total number of spermatogonia increased until late puberty to stabilize subsequently. Spermatocytes and spermatids appeared during puberty and increased dramatically until the end of this period. The germ cell ratios, indicative of spermatogenic efficiency, improved continuously in late puberty coincidentally with a reduction of spermatocyte degeneration. Sertoli cells proliferated in the neonatal and infantile periods, determining a longitudinal growth of the seminiferous tubules, but remained stable during puberty, when androgen-binding protein secretion increased significantly. The multiplication of germ cells is the main factor responsible for the increment in tubule diameter during puberty and determines the most noticeable postnatal modification of testicular volume. During late puberty, the reduction of spermatocyte degeneration leads to an increment in germ cell ratios and a progressive, but slow, improvement of spermatogenic efficiency, explaining why pubertal development of the testis occurs over such a prolonged period in this primate. This is in contrast to what happens in most laboratory animals and suggests that the Cebus is a useful model for studies of human male puberty.

Aging↗

Interovarian relationship in the secretion of progesterone during the luteal phase of the capuchin monkey (Cebus apella).

In basal conditions, progesterone concentrations were similar in the ovarian veins of the ovary +CL (3211 +/- 526 ng/ml) and the ovary -CL (3165 +/- 554 ng/ml), but after blocking the blood flow between the ovary +CL and the uterus, the progesterone values in the vein draining the ovary -CL decreased to 1218 +/- 394 ng/ml (P less than 0.01). When [3H]progesterone was injected in the ovary +CL, the radioactivity appeared earlier and more concentrated in the vein draining the ovary -CL (30 sec, 0.53% of injected dose) than in the femoral vein (150 sec, 0.08% of injected dose). Removal of the ovary +CL was followed by a brief maintenance of peripheral progesterone within luteal-phase levels. The in-vitro progesterone production by a suspension of cells isolated from the corpus luteum was 47.5 +/- 12.8 ng/ml/2 h, whereas luteal-like cells isolated from the ovary -CL secreted 14.3 +/- 6.0 ng/ml/2 h (P less than 0.01) into the medium. We therefore suggest that the symmetrical and high secretion rate of progesterone by the ovaries of the capuchin monkey indicates a between-ovary communication system, and that the luteal-like tissue of the ovary -CL can produce relatively large amounts of progesterone.

Animals↗

Direct assay of urinary steroid glucuronides for monitoring the approach of ovulation.

The concentrations of estrone-3-glucuronide (E(1)3G) and pregnanediol-3-glucuronide (P(2)3G) in daily samples of early morning urine (EMU) were correlated with the levels of estradiol (E2), progesterone (P) and LH in respective plasma samples. Forty-six menstrual cycles were studied, in order to determine the practical usefulness of the urine assays for detecting: a) an individualized estrogen concentration threshold value, announcing the approach of ovulation. b) an individualized signal provided by P(2)3G in urine from which it can be assumed that ovulation has already occurred. The results showed that the concentration of E2 in plasma, in any day of the cycle, can be precisely inferred from the respective concentration of E(1)3G in EMU. The estimation of the plasmatic P values from those of P(2)3G in EMU had to be based on different factors according to the phase of the cycle, fact that suggests the presence of a phase-related variation in the glucuronization of P metabolites. Considering three consecutive E(1)3G urinary assay results, it was possible to identify a threshold value termed Estrogen-Peak Initiating Rise (E-PIR), which anticipated in 3.02 +/- 0.18 days the occurrence of an LH peak. The attempts to detect the occurrence of ovulation by an individualized urinary P(2)3G signal proved disappointing. The signal was detected, either before, simultaneously or after the LH peak.

Adult↗

Normal and pathological electrocardiographic patterns in the Cebus monkey.

The normal electrocardiographic (ECG) pattern was determined for Cebus monkeys and compared with those obtained in animals subjected to experimental heart damage. ECG patterns were related to the anatomopathological findings in both normal and treated animals. The anatomic study revealed a vertical heart in which both ventricles constituted the frontal aspect. The experimental heart injury either through the inoculation of Trypanosoma cruzi or after the treatment with isoproterenol induced ECG changes which were correlated with specific anatomopathological lesions.

Animals↗

Rat brain norepinephrine release during progesterone-induced LH secretion.

The administration of 1.5 mg of progesterone to ovariectomized estrogen-primed rats induced a surge in plasma norepinephrine (NE) preceding the pituitary LH release. The injection of reserpine (2 mg/kg) 2 h prior to progesterone completely blocked the progesterone effects on both NE and LH plasma surges. On the other hand, the adminitration of phenoxybenzamine prior to progesterone, blocked the steroid effect on LH without inhibiting the plasma NE rise. Contrarily, the alpha-blocker was able to induce a rapid increase in the amine levels 2 h after its injection. The determination of NE in the anterior hypothalamus of these rats revealed that simultaneously with the plasma NE rise induced by progesterone there was a fall in the hypothalamic amine levels. Both reserpine and phenoxybenzamine caused a depletion in the amine content of the anterior hypothalamus. In experiments measuring the arteriovenous difference in the concentration of NE across the brain following progesterone-induced LH release, it was found that most NE comes from the brain. The amine rise was evident in the jugular vein while the arterial NE concentration showed a slight increase. These findings raise the possibility that the changes in circulating NE may reflect an enhanced noradrenergic activity occurring in the brain from which the LH surge results.

Animals↗

Plasma levels of norepinephrine during the periovulatory period in normal women. Further studies.

Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day -8 to day -4, and every 8 hours from day -3 to day +2; estradiol (E2), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E2 peak. These values remained high until 16 hours before the LH peak and decreased gradually, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge.

Anovulation↗

Plasma levels of norepinephrine (NE) during the periovulatory period and after LH-RH stimulation in women.

In three normally cycling women studied daily from day 10 to 17 of the menstrual cycle, the levels of circulating norepinephrine showed a sharp rise preceding or concomitantly with the ovulatory LH surge. In two patients the norepinephrine peak took place 24 hr. previously to the LH rise and in the third one it occurred simultaneously. The simultaneous determination of ovarian hormones and norepinephrine showed no temporal correlation between this catecholamine and either estradiol or progesterone. On the other hand, after a single intravenous 100 mug dose of LH-RH, a significant rise in plasma norepinephrine, preceding the LH peak, was found in the four patients studied. The determination of norepinephrine at 3 minute intervals beginning one minute after LH-RH injection showed a significant rise in the amine levels ranging from 5 to 10 times in respect to basal values between 1 and 6 minutes after LH-RH stimulation. In these patients a second peak of norepinephrine occurred simultaneously with the maximal response of LH, which rose to peak levels after 18 minutes in one patient and after 24 minutes in the other. These findings are discussed with respect to the origin and role of increased amounts of plasma norepinephrine related to the LH surge.

Estradiol↗

Plasma norepinephrine during the rat estrous cycle and after progesterone treatment to the ovariectomized estrogen-primed rat.

In four-day cycling rats studied during the estrous cycle, the levels of circulating norepinephrine (NE) showed a sharp rise concomitant with the LH surge in the afternoon of proestrus. Following the peak, plasma NE fell rapidly to the minimum value by the morning of estrus. The administration of progesterone to ovariectomized estrogen-primed rats resulted in a surge in plasma NE levels 4 h after progesterone treatment. The maximal levels attained were 3-fold greater than baseline values, falling rapidly to reach basal values 8 h after the administration of progesterone. The amine levels remained unaffected 12-20 h later. The LH values attained a maximum 8 h after the injection of progesterone. In rats treated with estradiol benzoate (EB) followed by 0.1 ml of oil instead of progesterone, neither the NE nor the LH peak were observed. These findings are discussed with respect to the significance of increased amounts of plasma NE related to the LH surge.

Animals↗

Time-dependence of estradiol effects on protein synthesis in the rat neurohypophysis.

The incorporation of 3H-leucine into neurohypophyseal proteins was measured in vitro, 24 h after the administration of a single dose of estradiol (0.3 mug) to castrated female rats. Estradiol treatment caused a significant increase of 3H-leucine incorporation into proteins of the posterior lobe. The effects of estradiol depended largely upon time injection. Rats injected at 06.00 h, i.e., at the end of the dark period exhibited a 74% increase in protein synthesis, whereas rat injected at 14.00 h, i.e., at the middle of the light period only showed a 30% of increase.

Animals↗