1. Hormones, Drugs, and Pregnancy Marsha Timmerman, LaSalle University Tracy Schatteman, Lincoln Land Community College Gretchen A. Koch, Goucher College Anton Weisstein, Truman State University

2. Goals Create a problem based learning module to teach students about hormones Three venues –Human A&P course: Reproductive system –Cell biology course: Cell signaling –Pharmacology course: Pharmacokinetics

3. Learning Objectives: Anatomy and Physiology Role of hormones in modulating female reproductive cycle Complexity of negative feedback mechanisms at the organismal level Pharmacology – intake, half-life, and excretion of medications Understand the public health implications of pregnancy and birth control

4. Learning Objectives: Cell Biology Structure and form of steroid molecules Role/function of steroid hormones on cellular level Specificity of cells – what makes a cell a target cell Cell signaling receptors Specificity of receptors – triggers and outcomes Applications to cancer on the cellular level

5. Problem Based Learning Concept Map The Hook: Initial case history of woman who gets pregnant on birth control pills Inquiry phase: students discuss and research into reproductive system, hormones and birth control pills. Students present what they have learned to the class. Case history part 2: Provides more information Investigative phase: students use tools such as Excel modules and AgentSheets to delve deeper into the subject. In this phase, each venue can move in the direction appropriate for the intent of their class.

6. Anatomy and Physiology Module Initial Case Bill walks into the student lounge and sees Amy sitting in a corner looking very dejected. Bill approaches Amy. Bill: “Hi Amy. You look upset. Is anything wrong?” Amy: “I guess. This morning I took a home pregnancy test, and it came up positive. I’m really shocked that I’m pregnant. I need to think about it for a while.” Bill: “Congratulations! I know that you and Ron have been talking about having a family. I did not realize that you had stopped using birth control.” Amy: “That’s the problem. I am still taking birth control pills; I think the one I am on is called Aygestin. Ron and I were thinking about a family but were not quite ready to take the plunge. I guess we don’t need to make the decision any longer.”

7. Anatomy and Physiology Module Step 2 Anticipated inquiries from initial student discussions –Can someone taking birth control get pregnant? –How does the reproductive system work? –How does birth control work? –What are hormones? –What is Aygestin? Students should work on their own to obtain answers to the above questions. Students need to present what they have learned to their group.

8. Anatomy and Physiology Module Step 3 More of the case… Amy goes to her doctor for a prenatal checkup. Amy: “I was taking my birth control pills as prescribed. The only time I missed one was a couple of weeks ago when I was up very late studying for an exam. After exams, Ron and I went away for a weekend get away to enjoy ourselves before the summer semester started.” Doctor: “Aygestin is a progesterone birth control pill. A woman’s reproductive system is controlled by a number of hormones that continually cycle.”

9. Female Reproductive Cycle

10. Feedback Mechanisms: Female Reproductive Hormones http://www.vrp.com/graphics /fem_repro_homeo.jpg

11. Reproductive Hormone ESTEEM Module Students can modify several conditions Chart automatically updates

12. Assumptions of the Reproductive Hormone Model Average 28 day menstrual cycle Does not include: GnRH, LH, estrogen Birth control pills: –Progesterone only (mini-pill) –Taken on days 1-21 –Placebo days 22-28 Progesterone –Suppresses FSH levels –Small release in follicular phase –Large release in luteal phase –Day 26: levels decline sharply Pregnancy blocks progesterone decline.

13. Pharmacokinetics Study of how drugs move through the body (1) Enter via ingestion, injection, absorption (1) Exit via excretion, metabolism (1) Possible Lesson: Birth control and hormones –How many doses can one skip before you get pregnant? –Must it correspond to the hormonal cycle?

14. A little mathematics… f(t) : the dosage function (2) Half-life rates: α and  g(t): concentration of drug in GI tract b(t) : concentration of drug in bloodstream GI Tract Blood Ingestion Decay in GI tract and absorption into blood Metabolism

15. Mathematical Equations Rate of change = Rate In – Rate Out The rate of change in the concentration of the drug in the GI tract is equal to the amount being ingested minus the concentration that is decaying. The rate of change in the concentration of the drug in the blood is equal to the concentration that is decaying from the GI tract minus the concentration decaying in the blood.

16. One Compartment Model Ingestion Blood Metabolism f(t) : the dosage function (2) Half-life rate: α b(t) : concentration of drug in bloodstream

17. Mathematical Equations Rate of change = Rate In – Rate Out The rate of change in the concentration of the drug in the blood is equal to the amount being ingested minus the concentration that is being metabolized.

18. Sliders to change dosage function dynamically. Sliders to change dosage function dynamically. User entry of drug half-lives User entry of drug half-lives Model description and assumptions Model description and assumptions Blood concentration versus GI concentration Time is still independent variable. Blood concentration versus GI concentration Time is still independent variable. Dosing Function Drug Concentrations Versus time Drug Concentrations Versus time

19. Comparisons of Steroids Cholesterol Progesterone Testosterone Estrogen

21. Future directions Elaborate and improve Hormone Module Public health applications –GapMinder, CDC Website Pharmacokinetics Modules –Documentation, Case Study, Sample Labs Model for cell signaling mechanisms –AgentSheets

22. Acknowledgements Tony Weisstein John Jungck Raina Robeva Michael Garman, Sean Lonsdale, David Ludgin, Kelley Moran, and Katrina Ramirez-Meyer Previous BioQUEST Participants

23. References 1.Aygestin® Product Insert, Duramed Pharm., Inc., Pomona, NY, July 2007 2.Drugs@FDA, http://www.accessdata.fda.gov/scripts/cder/drugsatfda/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ 3.Conneely, O. and B. Jericevic. Progesterone Regulation of Reproductive Function Through Functionally Distinct Progesterone Receptor Isoforms. Rev. in Endocrine & Metabolic Disorders 3:201, 2002 4.Menstrual cycle hormone animation, IAMSE http://www.healcentral.org/content/collections/McGill/MENSESANIMFINAL800x600.s wf http://www.healcentral.org/content/collections/McGill/MENSESANIMFINAL800x600.s wf 5.Physician Information for Depo-Provera Pharmacia & Upjohn Company, Kalamazoo, MI, Feb. 2004 6.Shughrue, P., D. Lubahn, A. Negro-Vilar, K. Korach, and I. Merchenthaler. Responses in the brain of estrogen receptor a-disrupted mice. PNAS, 94:11008, 1997 7.Spitznagel, E. (Fall 1992) Two-Compartment Pharmacokinetic Models C-ODE-E. Harvey Mudd College, Claremont, CA. 8.Wierman, M. Sex steroid effects at target tissues: mechanisms of action, Advan. Physiol. Edu. 31: 26-33, 2007 9.Wierman, M. http://www.the- aps.org/education/refresher/Wierman%20talk/player.htmlhttp://www.the- aps.org/education/refresher/Wierman%20talk/player.html 10.Yeargers, E.K., Shonkwiler, R.W., and Herod, J.V. (1996) An Introduction to the Mathematics of Biology. Birkhäuser.