9. Sex steroids: testosterone, oestrogen and progesterone Flashcards
what are the 5 KEY ROLES of SEX STEROIDS
*Promote SEXUAL DIFFERENTIATION (in utero and pubertal stage)
*Development of SECONDARY SEXUAL CHARACTERISTICS (puberty)
*Regulate sexual behaviour
*Supporting normal REPRODUCTIVE function
*Support BONE GROWTH and MAINTAIN BONE (and muscle) MASS
core STRUCTURE of SEX STEROIDS
Cyclopentanoperhydrophenanthrene ring (consists of 4 rings: A B C D)
also called the STEROID NUCLEUS or STERANE
what is the basic SUBSTRATE of the STEROIDOGENESIS PATHWAY
CHOLESTEROL (from blood stream)
how is CHOLESTEROL CONCERTED to PROGNENALONE in STEROIDOGENESIS PATHWAY
CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME
(CYP11A enzyme CLEAVES SIDE-CHAIN)
where does STEROIDOGENESIS PATHWAY take place (3)
- ADRENAL GLANDS
-OVARIES
-TESTES
what are formed from STEROIDOGENESIS PATHWAY (4) (using cholesterol)
- ALDOSTERONE (zona glomerulosa of adrenal cortex)
- CORTISOL (zona fasciculata of adrenal cortex)
- TESTOSTERONE
- ESTROGENS
in STEROIDOGENESIS PATHWAY:
most of the ENZYMES are part of which super FAMILY
CYP 450 super family
(except 3-beta HSD (dehydrogenase)
& 5-alpha reductase)
in STEROIDOGENESIS PATHWAY:
what is TESTOSTERONE CONVERTED to
DIHYDROTESTOSTERONE
- more POTENT form
or ESTROGENS
in STEROIDOGENESIS PATHWAY:
with which ENZYME is TESTERONE converted to DIHYDROTESTOSTERONE (important)
5-ALPHA REDUCTASE
in STEROIDOGENESIS PATHWAY:
how are ESTROGENS formed
CONVERSION of:
ADROSTENEDIONE or TESTOSTERONE
in STEROIDOGENESIS PATHWAY:
what are the 3 FORMS of ESTROGENS
ESTRONE
ESTRADIOL (major)
ESTRIOL
in STEROIDOGENESIS PATHWAY:
which ENZYME is used to CONVERT ADROSTENEDIONE and TESTOSTERONE to ESTROGENS
AROMATASE (aka estrogen synthetizing enzyme)
- aromatises A RING
in STEROIDOGENESIS PATHWAY:
ANDROSTENEDIONE is CONVERTED to which ESTROGEN (using aromatase)
ESTRONE
in STEROIDOGENESIS PATHWAY:
TESTOSEROME is CONVERTED to which ESTROGEN (using aromatase)
ESTRADIOL
in STEROIDOGENESIS PATHWAY:
which is the MAJOR ESTROGEN found in blood tests
ESTRADIOL
in STEROIDOGENESIS PATHWAY:
what are the CELLULAR LOCATIONS of the ENZYMES
SMOOTH ER (most)
MITOCHONDRIA
describe the action of STEROID HORMONES - GENOMIC ACTION
- enters through membrane
- BINDS with INTRANUCLEAR RECEPTOR (in nucleus)
- BINDS to DNA SEQUENCES
- creates HORMONE RESPONSE ELEMENT - induces TRANSCRIPTION of mRNA to produce SPECIFIC EFFECTOR PROTIENS which bring about physiological EFFECTS
where do STEROID HORMONES BIND
INTRANUCLEAR RECEPTORS
then to DNA SEQUENCES
EFFECT of STEROID HORMONES in
Skin
Bone
Teeth
Cardiovascular
Metabolic
Immune system (anti-
inflammatory effects)
how is NON-GENOMIC action opposed to GENOMIC action
FASTER
what happens in NON-GENOMIC ACTION
steroid hormone STIMULATES G-PROTEIN COUPLED RECEPTOR
- signal transduction, KINASE CASCADES
- lead to PHYSIOLOGICAL EFFECTS
COMMUNICATION between GENOMIC and NON-GENOMIC ACTION
NUCLEAR RECEPTORS in cytosol
- directly affect GROWTH FACTORS on MEMBRANE
- & can result in CALCIUM INFLUXES
cause PHYSIOLOGICAL EFFECTS
where is TESTOSTERONE produced in TESTICLES
LEYDIG CELLS
where is TESTOSTERONE produced in OVARIES
THECA INTERNA CELLS
TESTOSTERION SECRETION is CONTROLLED by which hormone
LH - LUTEINIZING HORMONE
what is LH (luteinizing hormone)
a PITUITARY GLYCOPROTEIN hormone
Testosterone secretion has pulsatile, diurnal and circadian rhythms:
when are the PEAKS and when is it lowest
PEAKS: EARLY MORNING (when wake up)
& MIDNIGHT
LOWEST: AFTERNOON, EVENINGS
FUNCTIONS of TESTOSTERONE
*During EMBRYONIC DEVELOPMENT , it regulates
the DIFFERENTIATION of the WOLFIANN DUCTS into EPIDIDYMIS, VAS DEFERENS
*It promotes SOMATIC GROWTH and VIRILISATION (development of male physical characteristics) in BOYS
*It is essential for maintaining SEXUAL FUNCTION & GERM CELL DEVELOPMENT (spermatozoa)
*It regulates SECONDARY SEXUAL/NON-SEXUAL CHARACTERISTICS and MUSCLE GROWTH
in Hypothalamic-pituitary-testicular axis:
role of HYPOTHALAMUS
releases GnRH - GONADOTROPIN RELEASING HORMONE to ANTERIOR PITUITARY
from GnRH PULSE GENERATOR in hypothalamus
Hypothalamic-pituitary-testicular axis:
how does the ANTERIOR PITUITARY respond to GnRH from hypothalamus
secretes LH (luteinising hormone) and FHS (follicle stimulating hormone)
Hypothalamic-pituitary-testicular axis:
what does LH from anterior pituitary act on
LEYDIG CELLS in TESTICLES
Hypothalamic-pituitary-testicular axis:
what do LEYDIG CELLS in testicles SECRETE in response to LH
ANDROGENS
Hypothalamic-pituitary-testicular axis:
effects of ANDROGENS (4)
- AROMATISED by aromatase enzyme into ESTROGENS
- stimulate SERTOLI CELLS
- NEGATIVE FEEDBACK affect on LH secretion from pituitary & INHIBIT GnRH Pulse Generator in Hypothalamus
- BEHAVIORAL EFFECTS ON CNS
Hypothalamic-pituitary-testicular axis:
what does FSH from the anterior pituitary act on
SERTOLI CELLS
‘nurse cells’
- nurse GROWTH and NURTURE of SPERMATAZOA
Hypothalamic-pituitary-testicular axis:
EFFECTS of SERTOLI CELLS
- AROMATISED into ESTROGENS by aromatase
- produce ANDROGEN-BINDING PROTEINS
- SPERMATOGENESIS
- NEGATIVE FEEDBACK EFFECTS in FSH - SECRETE INHIBINS
Hypothalamic-pituitary-testicular axis:
what do ANDROGEN BINDING PROTEINS do (from sertoli cells)
maintain conc. of testosterone in testicles
important for development of sperm (spermatogenesis)
What is a TESTICLE made up of
TESTICULAR LOBULES
what are TESTICULAR LOBULES of testes composed of
SEMNIFEROUS TUBULES
what cells are inside SEMNIFEROUS TUBULES
SERTOLI CELLS (nurse development of sperm between them)
what cells are found between SEMNIFEROUS TUBULES in INTERSTITION
LEYDIG CELLS (testoserone)
where is the PREDOMINANT PRODUCTION of ESTROGENS
in OVARIES by GRANULOSA CELLS
also produced locally in tissues
in which CELLS in the OVARIES is ESTROGEN produced
GRANULOSA CELLS
ESTRADIOL can also be PRODUCED by..
CONVERSION of circulating ANDROGENS by AROMATISATION
ESTROGEN SECRETION is under the influence of which hormones
LH and FSH
- GONADOTROPINS from anterior pituitary
FUNCTIONS of ESTROGEN (6)
*It regulates secondary sexual female
CHARACTERISTICS , & SEXUAL BEHAVIOUR
*It is responsible for SECRETORY ACTIVITY within
the GENITAL TRACT
*It regulates GnRH SECRETION , and is
responsible for OVULATION during a MENSTRUAL CYCLE
*Regulates CARDIOVASCULAR PHYSIOLOGY
and NEURONAL GROWTH,
BONE STRUCTURE and integrity
Hypothalamic-pituitary-ovarian axis (women):
role of HYPOTHALAMUS
release GnRH (GONADOTROPIN RELEASING HORMONE) to anterior pituitaary
Hypothalamic-pituitary-ovarian axis (women):
role of HYPOTHALAMUS
release GnRH (GONADOTROPIN RELEASING HORMONE) to anterior pituitary
Hypothalamic-pituitary-ovarian axis (women):
response of ANTERIOR PITUITARY to GnRH from hypothalamus
secretes LH and FSH
Hypothalamic-pituitary-ovarian axis (women):
what does LH from anterior pituitary act on
THECA CELLS (in ovarian follicle)
Hypothalamic-pituitary-ovarian axis (women):
what does FSH act on
GRANULOSA CELLS
Hypothalamic-pituitary-ovarian axis (women):
what do THECA CELLS SECRETE in response to LH (2)
ANDROGENS (act on granulosa cells)
PROGESTINS (progesterone-like hormones)
Hypothalamic-pituitary-ovarian axis (women):
what do GRANULOSA CELLS SECRETE in response to FSH (4)
- ESTROGENS
- add to PROGESTINS
- INHIBINS (negative feedback)
- ACTIVINS
what is ESTROGEN responsible for in MENSTRUAL CYCLE
OVULATION
what in the OVARY, MATURES, RUPTURES and DISCARCHES OOCYTE
GRAAFIAN FOLLICLE
what organ is formed in OVARY after RUPTURE
CORPUS LUTEUM (secretes progesterone)
what does the CORPUS LUTEUM become if no pregnancy
CORPUS ALBICANS
parts of FALLOPIAN TUBE
- Fimbriae (finger like)
- Infundibulum
- Ampulla
- Isthmus
what is the MAIN PROGESTIN
PROGESTERONE
what is PROGESTERONE secreted by
CORPUS LUTEUM (formed by ovary after ovulation)
PROGESTERONE is a pro… hormone
pro PREGANCY
FUNCTIONS of PROGESTERONE (7)
*It EMBEDS a FERTILISED OVUM and MAINTAINS PREGNANCY
*Induces DECIDUALIZATION of the ENDOMETRIUM (changes in preparation for pregnancy),
INHIBITS UTERINE CONTRACTIONS,
INCREASES VISCOSITY of CERVICAL MUCUS (prevent sperm entering)
promotes BREAST DEVELOPMENT,
INCREASES BODY TEMPERATURE
*It INHIBITS GnRH release
how does PROGESTERONE prevent fertilisation by further sperm
INCREASES VISCOSITY of CERVICAL MUCUS
MENSTRUAL CYCLE varies between how many days
28-35 DAYS
when does FOLLICULAR / PROLIFERATIVE PHASE begin (when an egg matures in ovaries)
with the BEGINNING of MENSES
how long does FOLLICULAR / PROLIFERATIVE PHASE last
14-21 DAYS
role of FSH in MENSTRUAL CYCLE (4)
- FOLLOCULAR RECRUITMENT
- FOLLICULAR GROWTH
- INCREASED ESTROGEN SECRETION
- appearance of LH RECEPTORS on GRANULOSA CELLS in preparation for LH SURGE
what are the 2 PHASES of the MENSTRUAL CYCLE
FOLLICULAR PHASE
LUTEAL PHASE
how long is the LUTEAL PHASE OF MENSTRUAL CYCLE
14 DAYS (constant)
what are the EFFECTS of ESTROGEN in the 2 PHASES
FOLLICULAR: STIMULATORY effect
- stimulates LH SURGE
- stimulates slight FSH SURGE
LUTEAL: INHIBITORY effect
- INHIBITS LH & FSH (therefore remain flat)
what happens in FOLLICULAR PHASE (before ovulation) in terms of HORMONE levels
- FSH INCREASE
(developmet of follicles and granulosa cells make estrogen) - ESTROGEN INCREASE & PEAK
stimulates - LH SURGE
- slight FSH surge
what is the LH SURGE ESSENTIAL for
RELEASE OF OVUM
- usually happens 36 hours after the surge
FORMATION or CORPUS LUTEUM
what is OVULATION TRIGGERED BY
RAPID RISE in ESTRADIOL LEVEL
positive feedback of
oestradiol at pituitary & hypothalamus results
in the LH surge
how are HORMONE LEVELS in LUTEAL PHASE of menstrual cycle
- PROGESTERONE LEVELS INCREASE
- ESTROGEN levels INCREASE again (secreted by Corpus Luteum)
- LH & FSH FLAT (inhibited by estrogen)
what is ESTROGEN SECRETED from in LUTEAL PHASE
CORPUS LUTEUM
LH PULSE FREQUENCY in FOLLICULAR PHASE opposed to in Luteal Phase
EVERY 90 MINUTES
( every 4 HOURS in luteal phase)
if PREGNANCY occurs then CORPUS LUTEUM is maintained by..
HCG secreted by TROPHOBLAST (placenta)
if no pregnancy, CORPUS LUTEUM DEGENERATED into… by…
CORPUS ALBICANS
by a process called LUTEOLYSIS
AROMATASE is an important enzyme in which pathway
STEROIDOGENESIS PATHWAY
AROMATASE is responsible for which 2 CONVERSIONS in peripheral tissues
- ANDROSTENEDIONE to ESTRONE
- TESTOSTERONE to ESTRADIOL
ANDROSTENEDIONE is converted to what by AROMATASE
ESTRONE
TESTOSTERONE is converted to what by AROMATASE
ESTRADIOL
AROMATASE is present in several tissues such as… (7)
GONADS
VASCULAR ENDOTHELIUM
ENDOMETRIUM
SKIN
BONE
BRAIN
ADIPOSE TISSUE
PLACENTA
AROMATASE DEFICIENCY (due to mutations in CYP19A1) can result in..
OVERPRODUCTION of TESTOSTERONE
& deficiency of estrogens
females affected by this are born with ambiguous genitalia
what is HYPOGONADISM
INABILITY of the TESTICLES / OVARIES to
PRODUCE TESTROSTERONE or ESTROGEN respectively
what is PRIMARY HYPOGONADISM due to
DEFECT at the level of the GONAD
i.e. the TESTICLES or the OVARIES
what is SECONDARY HYPOGONADISM due to
DEFECT at the level of the PITUITARY or HYPOTHALAMUS
- causing REDUCED amplitude or pulsatility of
FSH, LH or GnRH SECRETION
