Methoxychlor may cause ovarian follicular atresia and proliferation of the ovarian epithelium in the mouse.

Methoxychlor (MXC) is currently used to protect agricultural products from insects. Previous studies show that MXC adversely affects the ovary, but the target cells were not revealed by those studies. Therefore, the purpose of this study was to test the hypothesis that MXC induces ovarian changes by adversely affecting the antral follicles and the ovarian surface epithelium in the mouse. To test this hypothesis, cycling female CD-1 mice (39 days) were dosed with MXC (8, 16, or 32 mg/kg/day), kepone (KPN, 8 mg/kg/day, positive control), or sesame oil (vehicle control) via intraperitoneal injection for 10 or 20 days. Estrous cyclicity was evaluated daily via vaginal lavage. After dosing, ovaries were collected for histological evaluation of follicle numbers, atresia, and surface epithelial height. The results indicate that at the 20-day time point, MXC (32 mg/kg) and KPN (8 mg/kg) increased the percentage of atretic antral follicles (n= 4-9,p

Apolipoprotein E is a putative autocrine regulator of the rat ovarian theca cell compartment.

Apolipoprotein (apo) E inhibits androgen production by ovarian theca cells. We found that apo E, as a synthetic peptide mimicked the full-size protein, induced theca and interstitial cell (TIC) apoptosis indicated by pyknotic cell morphology, increased DNA end-labeling (TUNEL), and DNA ladders. None of the low-density lipoprotein (LDL) receptor superfamily members were involved because the universal antagonist of these receptors, receptor-associated protein (RAP), did not block apo E-induced apoptosis. Furthermore, several apo E synthetic peptides that do not bind the LDL receptor did induce TIC apoptosis. Similar to apo E, apoptogenic agents such as ceramide and LY 294002, a phosphatidylinositol (PI) 3-kinase inhibitor, induced apoptosis and suppressed androstenedione production. However, apoptosis alone was not responsible for apo E suppression of androstenedione production because both insulin and IGF-I prevented apo E-induced apoptosis, but neither restored androstenedione production. Theca cells of atretic follicles express the greatest apo E mRNA, and here we show that cultured TIC produce apo E. When considered with the observation of TUNEL-positive theca cells in atretic follicles these results support our hypothesis that intraovarian apo E controls theca cell production of androgen as well as limiting the size of the theca cell compartment.

Intra- and extracellular dehydration has no effect on plasma levels of angiotensin II in an amphibian.

Previous studies have demonstrated that both dehydration (intra and extracellular) and treatment with angiotensin II (A-II) induce changes in thirst-related behavior in the spadefoot toad, Scaphiopus couchii. One of the steps in determining a causal relationship between a hormone and a behavior is to determine that there is association between an animal's performance of the behavior and changes in endogenous hormonal concentrations. The hypothesis tested that plasma levels of the peptide hormone A-II would change as a result of dehydration known to induce water absorption response (WR) behavior in the spadefoot toad. Plasma samples were taken from toads dehydrated intracellularly by injection of hypertonic solutions of NaCl or sucrose at levels known to induce WR behavior. As an osmotic control, a group of animals was injected with urea, which has been demonstrated to not induce WR behavior. In order to determine the effects of extracellular dehydration on plasma, A-II levels in toads dehydrated by plasma volume depletion via cardiac puncture were compared to sham-punctured controls. None of the treatments in any experiment resulted in significant differences in plasma levels of angiotensin II among groups sampled at the time when WR behavior occurs. These results do not support the hypothesis that dehydration-induced thirst is stimulated by changes in plasma A-II concentrations at the onset of WR behavior. J. Exp. Zool. 286:343-349, 2000.

Intra- and extracellular dehydration-induced thirst-related behavior in an amphibian.

The behavioral response to dehydration is critical to an animal's survival. Because of their permeable skin, amphibians are particularly sensitive to dehydrating conditions. We tested the hypothesis that different forms of dehydration induce water absorption response (WR) behavior in the desert spadefoot toad, Scaphiopus couchii. First, we determined the behavioral response to intracellular dehydration by treating fully hydrated toads with increasing concentrations of hypertonic solutions of NaCl or sucrose via intraperitoneal injection (i.p.). Animals that were treated to induce intracellular dehydration with either solute exhibited a significant increase in WR behavior compared to vehicle-treated controls. To distinguish that the response was a result of an increased osmotic gradient between the intra- and extracellular compartments, we treated fully hydrated animals i.p. with urea, which freely passes into the intracellular compartment and increases overall animal osmolarity. Urea treatment did not induce WR behavior. To determine the response to extracellular dehydration, the blood volume of fully hydrated toads was reduced via cardiac puncture, and the WR behavior was measured. Animals who had a reduction in blood volume exhibited a significant increase in WR behavior compared to sham-punctured controls. Our results are the first to demonstrate that multiple forms of dehydration can induce thirst-related behavior in amphibians.