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Biomedical subjects

L Tyrey

Publications and source records attributed to L Tyrey.

61 records · Page 4Linked to original sources

Effect of atrazine on ovarian function in the rat.

The effect of the chlorotriazine herbicide, atrazine, on ovarian function was studied in Long-Evans hooded (LE-hooded) and Sprague-Dawley (SD) rats. Atrazine was administered by gavage for 21 d to females displaying regular 4-d estrous cycles. In both strains, 75 mg/kg/d disrupted the 4-d ovarian cycle; however, no distinct alteration (i.e., irregular cycles but not persistent estrus or diestrus) was apparent at this dose. At 150 mg/kg/d, atrazine induced repetitive pseudopregnancies in females of both strains. The highest dose tested (300 mg/kg/d) also induced repetitive pseudopregnancies in the SD females, while the ovaries of the LE-hooded female appeared regressed and the smear cytology was indicative of the anestrous condition. Although a NOAEL was not established, the doses employed in this experiment were in excess of those used in chronic feeding studies in which an early onset of mammary gland tumors was noted. These data demonstrate that atrazine can disrupt ovarian function and bring about major changes in the endocrine profile of the female.

Animals↗

Estrous cycle patterns of Sprague-Dawley rats during acute and chronic atrazine administration.

An increased incidence or earlier onset of mammary tumors (MT) has been associated with lifetime feeding of atrazine, an agricultural herbicide, to Sprague-Dawley (SD) female rats. Because MT occur spontaneously in this strain, along with episodes of persistent estrus and acyclic estrogen secretion, it was proposed that atrazine may act to promote this process. SD female rats, 7 to 8 wks old, were administered atrazine while vaginal cytology was monitored. At 200 mg/kg/d by gavage, which clearly exceeded the maximum tolerated dose (MTD), the predominant early response was prolonged vaginal diestrus. Persistent estrous episodes were seen, but less commonly. When atrazine was added to the diet, there was likewise an initial appearance of prolonged diestrus at 400 ppm, but by 13 to 14 wks on test (20 to 21 wks of age), persistent estrus was predominant, rising to >50% of animals by 26 wks on test. Age-matched controls also displayed persistent estrus, but to a lesser degree. At 400 ppm atrazine for 6 mo, animals displayed vaginal estrus for a mean of 62.8% of all days, versus 47.3% in age-matched controls, and 20 to 25% in young animals. The 400 ppm dose also exceeded the MTD. Observed no-effect levels for estrous cycling and body weight change were 50 ppm. Significant effects on estrous cycling occurred only at levels previously associated with enhanced or premature MT formation, and suggest that the tumor response in aging SD female rats can be manipulated by factors controlling the internal estrogen milieu. Because atrazine has no intrinsic estrogenic activity, it is more likely that high-level dosing to a susceptible animal model alters control of ovulation and normal cycling. The requirement of excessive dosing levels, as well as differences in neuroendocrine senescence, makes a risk to human health from this mode of action essentially nonexistent.

Aging↗

Gestational trophoblastic neoplasia.

As a result of modern diagnostic and therapeutic techniques, nearly 100 percent of patients with GTN can be cured of a disease thay only a few years ago had a high death rate. To achieve this, skillful mixing of chemotherapy, surgery, and irradiation, as well as supportive therapy, are necessary. Understanding and utilizing the HCG assay to monitor disease status is vital. With this approach, essentially all of these patients should survive, many to have successful future pregnancies.

Antineoplastic Agents↗

Placental villous glucose metabolism and hormone release respond to varying oxygen tensions.

OBJECTIVE: The effects of varying oxygen tensions on tissue metabolic behavior are not well understood, yet many intracellular pathways are influenced by them. In the placenta, optimal in vivo oxygen tension at the villous level is unknown. The purpose of this study was to determine effects of varying oxygen tensions on glucose metabolism and hormone release from perifused placental villous explants. METHODS: Placentas from term normal pregnancies (n = 8) were individually minced into villous fragments, placed into three parallel chambers for each placenta, and continuously perifused for 6 hours with nonrecirculating medium aerated with either 0%, 20%, or 95% oxygen yielding mean oxygen tensions of 76 mmHg, 167 mmHg, and 543 mmHg respectively. Outflow medium was removed at regular intervals and compared to the inflow medium to determine oxygen and glucose consumption as well as lactate, lactate dehydrogenase, hCG, estradiol, and progesterone release. RESULTS: Oxygen consumption was directly proportional to oxygen tension. Glucose consumption was lowest at low oxygen tension, while both lactate and LDH release were lowest at high oxygen tension. Both hCG and progesterone release rates were lowest at high oxygen tensions. Estradiol release demonstrated a trend similar to that of the other hormones although there was no statistically significant difference among the three different levels of oxygen tension. CONCLUSION: Varying oxygen tensions affect placental villous glucose metabolism and hormone release. Under lower oxygen tensions, glucose is metabolized through glycolysis rather than through oxidative phosphorylation and is associated with higher lactate release. Exposure to higher oxygen tensions results in reduced hCG and progesterone release. Higher oxygen tensions may be associated with tissue toxicity.

Chorionic Gonadotropin↗