Editor’s note: Science Scan is a roundup of recently published biotechnology-relevant research.
When the pituitary gland can’t manufacture human growth hormone (hGH), the result is dwarfism, or at least stunted growth. When the gland churns out an excess of hGH (aka somatotropin), diabetes ensues. Endocrinologists are baffled trying to determine what triggers production of hGH, which is vital for proper physical development.
Now scientists at the University of Pennsylvania School of Medicine in Philadelphia have found the mechanism that sets the hormone in action. What’s more, they’ve discerned an unusual activation pattern that operates by remote control.
They report their findings in the journal Molecular Cell, dated Feb. 15, 2002, under the title “A defined locus control region determinant links chromatin domain acetylation with long-range gene activation.” Working with transgenic mice, the co-authors have pinpointed the activation mechanism at a location called “hypersensitive site 1” (HS1) within the “locus control region” 14.5 kilobases away from the hGH gene. Within the microscopic realm of cells, the authors suggest, this long-distance activation is the equivalent of unlocking the front door of a house from seven buildings away.
What makes this remote-control discovery surprising is the fact that most genes are controlled by a promoter element adjacent or near the gene. But in this maverick case, that 14.5-kilobase gap is so far out that there’s an intervening gene between hGH and the activation site. The human gene cluster containing hGH, the team points out, includes five separate human growth genes, four of which do business during fetal development. Only the fifth hGH gene goes to work following the birth of the infant, and controls subsequent normal growth. When it fails on the job, the growing child develops pituitary dwarfism, in which stature never reaches 5 feet. The researchers point toward an eventual gene therapy approach to correct this type of dwarfism.
The study demonstrates that, unlike most hormones, hGH can’t be turned on merely by activating a nearby promoter element. Instead, turning on the HS1 triggers a series of enzymatic changes spanning the layer of proteins and DNA chromatin that separate the hypersensitive site from the gene’s promoter, and ultimately opening the hormone itself. They are now studying the mechanism through which the signal spreads.
How Male Newts Vie For Precedence In Sperm Selection By Female Via Topping Off’ Process
In newts and salamanders small, lizard-like amphibious vertebrates the battle of the sexes takes place in competition among males for which one’s sperm gets chosen first by the female. A paper in the Proceedings of the National Academy of Sciences (PNAS), dated Feb. 19, 2002, reports a novel process in this courtship ceremony. It’s titled: “Topping off: A mechanism of first-male sperm precedence in a vertebrate.” The article’s authors are zoologists at Oregon State University in Corvallis.
They describe their discovery of “topping off” as “a model in which a female accepts a large amount of sperm from her first mate, and if additional space remains in her thermathecae [sperm case or bank] she then seeks additional mates until she has no need for further sperm. Once this topping off’ of the female’s storage organ is complete, sperm from the males mix freely within it until they are used to fertilize the eggs as they are laid.”
The authors observe, “Sexual selection is an important facet of the evolutionary process. Although many of the key aspects of sexual selection occur before mating, research over the last three decades had led to the understanding that competition among sperm within a female’s reproductive tract can be vital to the ultimate outcome of mating competition.”
They make the point that much of this research has been conducted under laboratory conditions rather than in the animals’ natural environment as this team has now done. Their experimental amphibian was the rough-skinned newt (Taricha granulose). They cite several reasons why this species provides a useful model of sperm competition: “First, females receive sperm during a short receptive period at the beginning of the reproductive season. They then lay eggs singly over the course of several weeks to months, fertilizing them with stored sperm. Before insemination, the male must unclasp the female, to deposit a spermatophore a capsule containing spermatozoa. The unrestrained female then has the option of either picking up the spermatophore or moving away and ending courtship.”