Donald W. Pfaff, Ph.D.

Pfaff H

Donald W. Pfaff, professor and head of the Laboratory of Neurobiology and Behavior at The Rockefeller University, is a brain scientist who uses neuroanatomical, neurochemical, and neurophysiological methods to study the cellular mechanisms by which the brain controls behavior. His laboratory's research has proceeded through four steps to demonstrate how steroid hormone effects on nerve cells can direct natural, instinctive behaviors.

First, Pfaff is known for discovering exact cellular targets for steroid hormones in the brain. A system of hypothalamic and limbic forebrain neurons with sex hormone receptors, discovered in rodents, was later found to be present in species ranging from fish through primates. This hormone-sensitive system apparently is a general feature of the vertebrate brain. His lab recently found that "knocking out" the gene for the estrogen receptor in animals prevents female reproductive behavior. Surprisingly, that single gene deletion resulted both in masculinizing female animals and, counterintuitively, feminizing males' behavior.

Secondly, his lab at Rockefeller then worked out the neural circuitry for hormone-dependent female reproductive behavior, the first behavior circuit elucidated for any mammal. Third, he and his colleagues demonstrated several genes that are "turned on" by estrogens in the forebrain. Fourth, in turn, their gene products facilitate reproductive behavior. For example, the induction of one of them, the gene for the progesterone receptor, showed that the hormone estrogen could turn on another transcription factor important, in turn, for behavioral control. Regulated gene expression in the brain participates in the control of behavior.

Taken together, these four advances proved that specific chemicals acting in specific parts of the brain determine individual behavioral responses.

While two genetic transcription factors, the estrogen and progesterone receptors, cooperate with each other to promote reproductive behavior, another transcription factor, the thyroid hormone receptor, actually interferes with estrogenic actions. Seasonal environmental changes, raising thyroid hormone levels, can block reproductive behaviors when they would be biologically inappropriate.

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