March 22, 2002

UCSD Team Reviews Pituitary Gland Development,
From a Common Primordium to Distinct Cell Types

Development of the anterior pituitary gland, from a common primordium in the roof of the embryonic mouth into an organ comprising multiple distinct endocrine cell types, is described by two University of California, San Diego (UCSD) School of Medicine researchers in a review published March 22, 2002 in the journal Science.

M. Geoffrey Rosenfeld, M.D., Howard Hughes Medical Institute investigator and UCSD professor, and Kathleen M. Scully, Ph.D., postdoctoral fellow, UCSD Department of Medicine, provide a step-by-step description of the intricate cell signaling and nuclear events that take place during key steps in pituitary gland development.

Lying at the base of the brain, the pituitary is a pea-sized gland that secretes hormones involved in growth, reproduction, lactation, thyroid gland function, and the maintenance of homeostasis (i.e. a constant internal environment). The gland is a complex organ regulating a combination of neural signals from the hypothalamus as well as feedback from target organs.

"In recent years, researchers have begun to identify some of the molecules that direct the series of developmental steps by which precursor cells gain a pituitary identity, proliferate, and differentiate to form the distinct hormone-producing cell types of the mature gland," Scully says.

In their Science review article, the researchers describe an initial external signaling phase where cells surrounding the pituitary primordium secrete molecules that start the developmental process. Eventually, the developing gland itself begins secreting some of these molecules, which help to establish its identity and facilitate growth. During this time, expression of certain transcription factors, that function as molecular switches turning genes on and off, must be activated or repressed in order for the pituitary gland to progress to the next step in its development.

Referring to their own genetic and biochemical research, as well as work by others, Rosenfeld and Scully note that pituitary gland development is controlled by complex interactions among a series of transcriptional regulatory factors.

"We know there isn't a single dedicated transcription factor for each gene. Instead, a combination of factors binding to the unique DNA sequence of each target gene is required," Scully says.

Among the research mentioned in the article is work from the Rosenfeld lab on Pit-1, a homeodomain transcription factor that activates three genes encoding the hormones prolactin, growth hormone and thyrotropin, each of which is made by a different type of cell in the pituitary gland. In this case, the interactions of Pit-1with other factors are dictated by target gene sequence resulting in the expression of only one gene in each cell type.

The researchers note that some of the molecular mechanisms that regulate gene expression and lead to terminal differentiation of distinct cell types in the pituitary gland may be used to solve the same type of developmental problems in other organs of the body.

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