New fertility-regulating hormone discovered - C&EN Global Enterprise

7 Nov 2010 - A new hormone that helps regulate fertility in mammals has been discovered independently by two groups of researchers at Salk Institute, ...
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Fungicide Chemistry Advances and Practical Applications

"V Maurice B. Green, Editor Independent Consultant Douglas A. Spiker, Editor Mobay Corporation Discusses exciting current research in the area of fungicides, with a special emphasis on the unique azole fungicides and their mode of action as ergosterol biosynthesis inhibitors. Provides valuable information on the history of azole chemistry and on the impact of azoles and the control of fungal pathogens of plants. Presents many practical uses of these fungi­ cides in disease control strategies. CONTENTS The History of Azole Chemistry · Biochem­ ical Mode of Action of Fungicides: Ergosterol Biosynthesis Inhibitors · Uptake and Translo­ cation of Carbon-14-Labeled Fungicides in Cereals: Macro- and Microautoradiographic Studies · The Pathogenesis of Plant Dis­ eases: The Effect of Modern Fungicides · Progress in the Chemical Control of Diseases Caused by Oomycetes · Control of Fungal Plant Diseases by Nonfungicidal Compounds • Control of Cereal Diseases with Modern Fungicides in Western Europe · Fungicides and Wheat Production Technology: Advances in the Eastern United States · Tree Fruit Crops: Potential Role for New Fungicides in the Eastern United States · Fungicides for Disease Control in Grapes: Advances in Development · Advances in Fungicide Chemistry and Fungal Control: Summary and Comments Developed from a symposium sponsored by the Division of Pesticide Chemistry of the American Chemical Society ACS Symposium Series No. 304 173 pages (1986) Clothbound LC 86-1248 ISBN 0-8412-0963-4 US & Canada $39.95 Export $47.95 Order from: American Chemical Society Distribution Dept. 9 1155 Sixteenth St., N.W. Washington, DC 20036 or CALL TOLL FREE 800-424-6747 and use your credit card!

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July 7, 1986 C&EN

New fertility-regulating hormone discovered A new hormone that helps regulate fertility in mammals has been dis­ covered independently by two groups of researchers at Salk Insti­ tute, La Jolla, Calif. Research teams led by Wylie Vale and Roger Guillemin have each isolated and puri­ fied from pig ovaries a protein very similar in size and structure to the ovarian protein inhibin. The func­ tions of the two proteins, however, seem to be exactly opposite: Inhibin suppresses the secretion of folliclestimulating hormone, or FSH, and the new protein stimulates it [Nature, 321,776 and 779 (1986)]. Inhibin itself was identified and characterized by Guillemin's group only last year. It has been found in two forms, called A and B, which share a common α-subunit with a molecular weight of about 18,000. Each form of inhibin has a second subunit, called β, connected to the first one by disulfide bonds. The β-subunits are related but distinct in the two forms of inhibin. Inhibin has been found in the gonadal fluids of several species of mammals. Its function seems to be to inhibit the pituitary gland from secreting FSH. When it is secreted, FSH causes the compartment around an egg cell, called a follicle, to grow and mature, a condition that is nec­ essary for the egg inside the follicle to mature. Both Guillemin and Wylie noticed in purifying inhibin a related sub­ stance that stimulated, rather than inhibited, FSH secretion. Guille­ min's group calls this second sub­ stance activin and Vale's calls it follicle-stimulating hormone releas­ ing protein or FRP. Both groups agree that it is a peptide of about 24,000 molecular weight, composed of two identical peptide chains linked by disulfide bridges. Both groups also find that the subunit in their newly isolated protein is the /3A-subunit of inhibin. The reproductive system seems to contain "a novel and complex regu­ latory system involving differential subunit association giving rise to dimers with biologically opposite effects," say Vale and his cowork­ ers. "It is clearly important to eluci­ date the conditions that determine

whether inhibin /3A-subunits are combined with the dissimilar in­ hibin α-subunits to yield inhibin, which suppresses FSH production, or with each other, yielding FRP, a potent stimulator of FSH produc­ tion," they continue. Earlier work in Guillemin's labo­ ratory has shown that each of the subunits—α, βΑ, and jSB—is pro­ duced at the direction of its own messenger RNA. Thus, they are dif­ ferent gene products, not process­ ing variations of some shared pre­ cursor protein. "If such rearrange­ ments of several gene products are the norm, rather than the excep­ tion, this process clearly considera­ bly extends the diversity of final products (and of their biological ac­ tivity) derived from a limited num­ ber of genes," Guillemin and co­ workers say. "Multiple arrangements of protein subunits through disul­ fide bridges, leading to mature mol­ ecules with totally different biolog­ ical activities (possibly of opposite biological activities, as here), would seem to extend to the gene products the possibility of reorganizations, as is now well recognized occurs in DNA and RNA," they suggest. The new protein should be a prime candidate for treating infer­ tility in women, says William A. Sadler, chief of the reproductive sci­ ences branch of the National Insti­ tute of Child Health & Human De­ velopment, a part of the National Institutes of Health. "From a medi­ cal point of view, this substance could be used to treat infertility in women that is caused by insuffi­ cient FSH secretion," he suggests. The National Institute of Child Health & Human Development supported both Vale and Guillemin's research. FSH production can also be stim­ ulated by another hormone, gonadotrophin-releasing hormone, or GnRH, produced by the hypothala­ mus. The new protein is more spe­ cific in its action than GnRH, which stimulates production of a second hormone, luteinizing hormone, as well as FSH. Such specificity makes it a better candidate for treating cer­ tain types of infertility, Sadler says. Rebecca Rawls, Washington