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Effects of Continuous Estradiol Administration by Polydimethylsiloxane and Paraffin Implants on Serum Hormone Levels and Uterine Responses

Departments of Pharmacology and Interdisciplinary Toxicology and Biochemistry, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

W. S. Branham

Department of Health and Human Services, Food and Drug Administration, National Center for Toxicological Research, Division of Teratogenesis Research, Jefferson, Arkansas.

R. Gutierrez-Cernosek

Beckman Instruments, Fullerton, California.

S. F. Cernosek, Jr.

Beckman Instruments, Fullerton, California.

Since tonic elevated estrogen levels are associated with toxic responses, including tumor promotion, we investigated the effects of continuous estradiol (E₂) administration by paraffin or polydimethylsiloxane (Silastic) implants on pituitary and uterine responses. Ovariectomized (OVEX) Sprague-Dawley rats implanted with low-dose (P₁) or high-dose (P₂) paraffin pellets showed initial high serum E₂ levels that decayed rapidly. Silastic implants provided more constant pharmacological serum E₂ levels during the 14 days of exposure. Rising serum LH and FSH levels in OVEX controls were suppressed by all E₂ implants. Serum prolactin levels, low in OVEX controls, rose after implantation (P₁ and P₂) but decayed to control values by 14 days. Prolactin induced by pharmacological E₂ levels initially rose, dropped by 72 hours, but again rose at later times. Uterine weight, low in OVEX controls, was increased by all implants. At later times, paraffin implants did not appear to release significant amounts of E₂. However, removal of P₂ implants from donors followed by transfer to new recipients stimulated uterine growth in recipients. All implants increased uterine DNA and RNA levels and the RNA/DNA ratio during the first 24–48 hours, followed by maintenance of elevated values. Poly(A)-containing RNA, isolated by oligo(dT) cellulose chromatography, comprised a constant percentage of RNA at all hormone levels and treatment times, suggesting a coupling of total RNA and poly(A)-containing RNA accumulation. Results are discussed in relation to the carcinogenic properties of estrogens, known to be correlated with continuous exposure to elevated estrogen levels.

International Journal of Toxicology, Vol. 3, No. 4, 303-316 (1984)
DOI: 10.3109/10915818409009085


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