Scientific Publications by FDA Staff

Int J Toxicol 1984 Jul;3(4):303-16

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

Sheehan DM, Branham WS, Gutierrez-Cernosek R, Cernosek SF Jr

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.