Hypothalamus, pituitary, and subordinate glands

Transcription

1 Endocrine System The endocrine system is the body s slow communication system relying on three main components Endocrine glands, such as hypothalamus, pituitary, thyroid, adrenal, pancreas, gonad Hormones circulating via blood Receptors and signal transmitters in target cells

2 Hypothalamus, pituitary, and subordinate glands

3 Hypothalamus Pituitary - Gonadal Axis in the Human Male

4 Endocrine Disrupting Chemicals (EDCs) Dichlorodiphenyltrichloroethane (DDT) Nonylphenol Polychlorinate Biphenyls (PCBs) Bisphenol A (BPA)

5 Endocrine Disruptor An endocrine disruptor is an exogenous substance that alters the function of the endocrine system, causing adverse health effects in an intact organism or its progeny. An endocrine disruptor may Mimic a hormone (agonistic effect) Block a hormone receptor (antagonistic effect) Interfere with the synthesis, transport, or breakdown of a hormone (metabolistic effect)

6 Major EDCs and Their Intended Uses Dichlorodiphenyltrichloroethane (DDT): Insecticide, used widely in agriculture until banned in the U.S. in 1972 and subsequently worldwide. Limited use to control vectors of disease, such as malaria Nonylphenol: Widely used as detergent, emulsifier, surfactant in industrial processes, also for cosmetics and household products. Polychlorinate Biphenyls (PCBs): Manufactured mostly as cooling and insulating fluids for industrial transformers and capacitors. Now banned but very persistent in environment Bisphenol A (BPA): Used as monomer in polycarbonate plastic and epoxy resins that are often present as inner coatings in food cans.

7 Major Books on EDCs Carson R. (1962) Silent Spring. Houghton Miflin Rachel Carson ( ) was a scientist in the U.S. Bureau of Fisheries before she became a science writer. Colborn T., Dumanoski D., Myers J.P. (1996) Our Stolen Future. New York: Penguin Books USA Inc. Theo Colborn is a Professor of Zoology at the University of Florida, Gainesvillle. She is also President of The Endocrine Disruption Exchange (TDEX), based in Paonia, Colorado.

8 Update 25.1 The concerns about EDCs are winding their way into legislation only slowly because (1) the combinatorial action of many EDCs makes it difficult to identify any single one as the main cause, and (2) the removal of EDCs from the environment is costly. For instance, for a town of 250,000 people, removal of estrogen mimics released by women using contraceptive pills would cost $10 million in water work upgrades and $0.8 million in yearly operation (Owen, 2012).

9 General model for gene activation by certain steroid hormones The target cells of steroid hormones have receptor proteins to which the hormones bind. The receptors of some steroids (including progesterone and testosterone) are located in the cytoplasm. These hormones displace an inhibitory protein, and the hormone-receptor complex enters the nucleus. The complex binds to an enhancer (steroid response element) as a dimer, causing active transcription.

10 Combinatiorial action of EDCs on transcription in eukaryotes Promoter elements such as the TATA box interact with a complex of proteins (green) that position the RNA polymerase next to the transcription start site. The transcription complex may be stabilized by activator proteins (pale purple) bound to response elements located further upstream. The stabilizing effects of activators may be compromised by endocrinedisrupting chemicals (EDC1 and EDC2, red).

11 Combinatorial effect of transcriptional activators (a) Two transcriptional activators binding to different response elements interact with the basal transcription complex, causing active transcription. (b) If activator 2 is inactivated or displaced by an excess of activator 1 there is no interaction with the transcription complex and only a basal level of transcription.