PHAR 300 Lecture 3: 3 PHAR300 - Contraceptives
7 Jun 2018
School
Department
Course
Professor
PHAR300
Contraception : a global perspective
-for women
-one of the most commonly prescribed drugs
Family planning
-concern to many individuals and families
-projective to be a huge increase in the world population
-where people use contraceptives : huge differences
depending on geography -> low use in Africa,
compared to the US
-France : huge use of the pill
-UK : lots of pills and male condoms
-US : lot of sterilisation (both male and female)
-=> no right or wrong answer, for any culture or
any individual, people make different choices
depending on their background
-kinds of contraceptives :
-pregnancy rate after 1 year of exposure : 85%
without using contraception
-spermicide alone 26%
-vaginal ring 1-2% => dramatic drop because of
steroids -> these contraceptives do more than a
physical barrier, they alter the hormonal control
Female reproductive tract
-women born with all the germ cells they will ever have
-follicle development during puberty ; ovulation 1/month (sometimes 2)
-once ovulated -> enter the follopian tube to the uterus where a fertilised oocyte can implant (if no
fertilisation -> menstruation)
-estrogens and progestins as drugs
-analogs of these hormones
-fertility control : contraception or ovulation induction
-hormone replacement therapy (after menopause)
-cancer chemotherapy (used as antagonists)
-others
-hypothalamic-pituitary-ovarian axis
-hypothalamus release GnRH (peptide hormone,
number of AA) in the portal circulation to the pituitary
-> will interact with gonadotropes in the anterior
pituitary -> triggers the release of LH and FSH
-these hormones react with receptors in the ovary,
granulosa cells and theca cells (steroidogenic cells)
produce estrogen and progesterone -> can negatively
feedback at the level of the hypothalamus and the
anterior pituitary
-GmRH secretion is pulsatile -> give additional
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information than just having a low continuous level
-pulsatile LH and FSH stimulate maturation of the ovarian follicle and steroid synthesis
-tell primary follicles to develop
-FSH regulates
-follicle growth and maturation
-cholesterol side chain cleavage (to make steroids) and aromatase activity in granulosa cells
(convert androgens to estrogen : testosterone to estrodiol inside the granulosa cells) =
steroidgenesis
-outside theca cells talk to each other
-yellow looking fluid : antrum (secondary follicles),
with the granulosa cells layer
-corpus luteum produces lots of steroids to maintain
pregnancy if the oocyte is fertilised
-mural cells around the walls and cumulus cells around
the oocyte
-LH : acts on theca cells to increase steroid synthesis and
increase FSH receptors => cooperative
-steroidogenesis : start with cholesterol, side chain cleavage
to make progesterone, converted to testosterone and then
aromatase reaction makes estradiol (aromatic ring) from
testosterone
-steroid hormone receptor homologies
-big family
-glucocorticoid receptor hGR, androgens, progesteron
receptor, 2 estrodial receptors hERalpha and hERbeta
-differences in ligand binding domain, DNA binding
domain and N-terminals
-estrogen action : bound to binding proteins in circulation,
lipophilic, interacts with estrogen receptor, binds DNA at
the estrogen response elements, turns on the expression of
genes depending on how much estrogen and what
coactivators are there
-alpha and beta : lots of similarities, but different
response elements and co-activators ; other non-
genomic mechanisms
-some tissue specificity : estrogen stimulates both receptors, but maybe we could find
analogues that are more specific (alpha or beta agonists)
-estrogen receptors in the brain, affect moodiness, can regulate temperature control (if no
estrogen -> hot flashes) ; systemic effects (blood clotting…) ; effects on the endometrium of
the uterus (build up of the lining depends on estrogen) ; mammary gland development, bone
maturation…
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Document Summary
One of the most commonly prescribed drugs. Projective to be a huge increase in the world population. Where people use contraceptives : huge differences depending on geography -> low use in africa, compared to the us. France : huge use of the pill. Uk : lots of pills and male condoms. Us : lot of sterilisation (both male and female) => no right or wrong answer, for any culture or any individual, people make different choices depending on their background. Kinds of contraceptives : without using contraception. Pregnancy rate after 1 year of exposure : 85% Vaginal ring 1-2% => dramatic drop because of steroids -> these contraceptives do more than a physical barrier, they alter the hormonal control. Women born with all the germ cells they will ever have. Follicle development during puberty ; ovulation 1/month (sometimes 2) Once ovulated -> enter the follopian tube to the uterus where a fertilised oocyte can implant (if no.
