CD20 Endocrine

Question 1

What is a common observation in rodent models when thyroid hormone homeostasis is disrupted?
A. increased incidence of thyroid tumors
B. disruption in body temperature maintenance
C. reductions in overall animal body weight
D. Due to reserve capacity of the thyroid, hormone disruption does not result in observable toxicity.

Answer 1

A. increased incidence of thyroid tumors

Explanation and Reference:
A reduction of thyroid hormone concentrations and increased thyroid-stimulating hormones have shown to induce neoplasia in the rodent thyroid. C&D 8th, pp. 412-413.

Question 2

How do thiocyanate and perchlorate affect the thyroid?
A. inhibition of thyroid peroxidase
B. inhibition of iodide transport
C. inhibition of thyroid hormone secretion
D. stimulation of the sodium-iodide symporter

Answer 2

B. inhibition of iodide transport

Explanation and Reference:
Perchlorate competitively blocks iodide from entering the thyroid by an effect on the Na+/I- symporter thus preventing the further synthesis of thyroid hormone. C&D 9th, pp. 992, 1339

Question 3

Why is the adrenal cortex predisposed to the toxic effects of many hydrophobic xenobiotic chemicals?
A. a lack of cytochrome P450 enzymes
B. pituitary hormone actions
C. bioactivation of long chain aliphatic compounds
D. large stores of lipids

Answer 3

D. large stores of lipids

Explanation and Reference:
Adrenal lipophilic steroid hormones are so hydrophobic they must be bound to serum lipids to be transported. The adrenal cortex is predisposed to the toxic effects of xenobiotic chemicals for three reasons. 1. the adrenocortical cells contain large stores of lipids for steroidogenesis. 2. membranes of the adrenocortical cells contain high levels of unsaturated fatty acids that are susceptible to the generation of reactive species such as free radicals via lipid peroxidation. 3. adrenocortical cells express enzymes involved in steroidogenesis, including those of the cytochrome P450 (CYP) family, which are capable of metabolizing xenobiotic chemicals to reactive toxic species. Thus the adrenals are particularly sensitive to hydrophobic xenobiotics. C&D 9th, pp. 977, 981

Question 4

Through what actions do both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) function as environmental endocrine disrupters?
A. retinoid agonists
B. estrogen antagonists
C. Ah receptor agonists
D. androgen agonists

Answer 4

C. Ah receptor agonists

Explanation and Reference:
The common mechanistic pathway for both TCDD and PCBs with regard to endocrine disruption is binding to the aryl hydrocarbon receptor (AHR). The AHR is a cytosolic nuclear transcription factor expressed in many tissues. Binding of xenobiotics to the AHR can affect many normal functions including the immune system and in utero development. See Endocrine Disruptor Screening Program at EPA [http://www.epa.gov/endo/] C&D 8th, p. 884; C&D 9th, pp. 318-320, 1438-1440.

Question 5

What can cause follicular cell adenoma formation in the rat thyroid?
A. iodine-catalyzed free radical production
B. secondary induction of thyroperoxidase
C. excessive secretion of TSH
D. retarded metabolism of T3 to T4 in peripheral tissues

Answer 5

C. excessive secretion of TSH

Explanation and Reference:
Excessive secretion of TSH can act in a proliferating manner. C&D 9th p. 454

Question 6

What event or mechanism describes endocrine disruptors?
A. results in increased sperm counts in humans
B. no effect on reproductive tract organogenesis
C. receptor competition or inhibition of steroidogenesis
D. affects only female reproduction

Answer 6

C. receptor competition or inhibition of steroidogenesis

Explanation and Reference:
Endocrine active chemicals are exogenous chemicals that exert their primary toxic effects via modification of hormonal responses, at relatively low doses that are not seen at higher doses. Diverse mechanisms have been proposed to eplain the shape of the nonmonotonic dose-response curves for endrocrine active chemicasls, including dose-dependent cycotoxicity, cell- and tissue-specific receptors and cofactors, receptor selectivity and down-regulation, receptor competition, and endocrine negative feedback loops. C&D 9th p 40

Question 7

What is the difference in effects between humans and rodents following prolonged elevation of Thyroid Stimulating Hormone?
A. In rodents, there is an increase in development of thyroid neopasia and follicular tumors. No effects in humans due to the negative feedback loop of TSH regulation.
B. There is no difference, both result in thyroid neoplasia.
C. There are no effects in rodents, but humans develop a reversible enlargement of the thyroid gland (goiter).
D. In rodents, there s an increase in the development of thyroid follicular tumors. In humans, a reversible enlargement of the thyroid gland (goiter).

Answer 7

D. In rodents, there s an increase in the development of thyroid follicular tumors. In humans, a reversible enlargement of the thyroid gland (goiter).

Explanation and Reference:
TSH increases in rodents commonly result in increased follicular cell hypertrophy, hyperplasia, and often neoplasia. In humans, increased TSH can result in a reversible increase in the thyroid gland (i.e., goiter). C&D 9th p327