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ENDOCRINOLOGY > 9. Sex steroids: testosterone, oestrogen and progesterone > Flashcards

9. Sex steroids: testosterone, oestrogen and progesterone Flashcards

1
Q

what are the 5 KEY ROLES of SEX STEROIDS

A

*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

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2
Q

core STRUCTURE of SEX STEROIDS

A

Cyclopentanoperhydrophenanthrene ring (consists of 4 rings: A B C D)

also called the STEROID NUCLEUS or STERANE

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3
Q

what is the basic SUBSTRATE of the STEROIDOGENESIS PATHWAY

A

CHOLESTEROL (from blood stream)

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4
Q

how is CHOLESTEROL CONCERTED to PROGNENALONE in STEROIDOGENESIS PATHWAY

A

CHOLESTEROL SIDE-CHAIN CLEAVAGE ENZYME

(CYP11A enzyme CLEAVES SIDE-CHAIN)

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5
Q

where does STEROIDOGENESIS PATHWAY take place (3)

A
  • ADRENAL GLANDS
    -OVARIES
    -TESTES
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6
Q

what are formed from STEROIDOGENESIS PATHWAY (4) (using cholesterol)

A
  • ALDOSTERONE (zona glomerulosa of adrenal cortex)
  • CORTISOL (zona fasciculata of adrenal cortex)
  • TESTOSTERONE
  • ESTROGENS
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7
Q

in STEROIDOGENESIS PATHWAY:
most of the ENZYMES are part of which super FAMILY

A

CYP 450 super family

(except 3-beta HSD (dehydrogenase)
& 5-alpha reductase)

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8
Q

in STEROIDOGENESIS PATHWAY:
what is TESTOSTERONE CONVERTED to

A

DIHYDROTESTOSTERONE
- more POTENT form

or ESTROGENS

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9
Q

in STEROIDOGENESIS PATHWAY:
with which ENZYME is TESTERONE converted to DIHYDROTESTOSTERONE (important)

A

5-ALPHA REDUCTASE

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10
Q

in STEROIDOGENESIS PATHWAY:
how are ESTROGENS formed

A

CONVERSION of:
ADROSTENEDIONE or TESTOSTERONE

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11
Q

in STEROIDOGENESIS PATHWAY:
what are the 3 FORMS of ESTROGENS

A

ESTRONE
ESTRADIOL (major)
ESTRIOL

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12
Q

in STEROIDOGENESIS PATHWAY:
which ENZYME is used to CONVERT ADROSTENEDIONE and TESTOSTERONE to ESTROGENS

A

AROMATASE (aka estrogen synthetizing enzyme)

  • aromatises A RING
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13
Q

in STEROIDOGENESIS PATHWAY:
ANDROSTENEDIONE is CONVERTED to which ESTROGEN (using aromatase)

A

ESTRONE

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14
Q

in STEROIDOGENESIS PATHWAY:
TESTOSEROME is CONVERTED to which ESTROGEN (using aromatase)

A

ESTRADIOL

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15
Q

in STEROIDOGENESIS PATHWAY:
which is the MAJOR ESTROGEN found in blood tests

A

ESTRADIOL

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16
Q

in STEROIDOGENESIS PATHWAY:
what are the CELLULAR LOCATIONS of the ENZYMES

A

SMOOTH ER (most)

MITOCHONDRIA

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17
Q

describe the action of STEROID HORMONES - GENOMIC ACTION

A
  • 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
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18
Q

where do STEROID HORMONES BIND

A

INTRANUCLEAR RECEPTORS

then to DNA SEQUENCES

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19
Q

EFFECT of STEROID HORMONES in

A

Skin
Bone
Teeth
Cardiovascular
Metabolic
Immune system (anti-
inflammatory effects)

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20
Q

how is NON-GENOMIC action opposed to GENOMIC action

A

FASTER

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21
Q

what happens in NON-GENOMIC ACTION

A

steroid hormone STIMULATES G-PROTEIN COUPLED RECEPTOR

  • signal transduction, KINASE CASCADES
  • lead to PHYSIOLOGICAL EFFECTS
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22
Q

COMMUNICATION between GENOMIC and NON-GENOMIC ACTION

A

NUCLEAR RECEPTORS in cytosol
- directly affect GROWTH FACTORS on MEMBRANE

  • & can result in CALCIUM INFLUXES

cause PHYSIOLOGICAL EFFECTS

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23
Q

where is TESTOSTERONE produced in TESTICLES

A

LEYDIG CELLS

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24
Q

where is TESTOSTERONE produced in OVARIES

A

THECA INTERNA CELLS

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25
Q

TESTOSTERION SECRETION is CONTROLLED by which hormone

A

LH - LUTEINIZING HORMONE

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26
Q

what is LH (luteinizing hormone)

A

a PITUITARY GLYCOPROTEIN hormone

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27
Q

Testosterone secretion has pulsatile, diurnal and circadian rhythms:
when are the PEAKS and when is it lowest

A

PEAKS: EARLY MORNING (when wake up)
& MIDNIGHT

LOWEST: AFTERNOON, EVENINGS

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28
Q

FUNCTIONS of TESTOSTERONE

A

*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

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29
Q

in Hypothalamic-pituitary-testicular axis:
role of HYPOTHALAMUS

A

releases GnRH - GONADOTROPIN RELEASING HORMONE to ANTERIOR PITUITARY

from GnRH PULSE GENERATOR in hypothalamus

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30
Q

Hypothalamic-pituitary-testicular axis:
how does the ANTERIOR PITUITARY respond to GnRH from hypothalamus

A

secretes LH (luteinising hormone) and FHS (follicle stimulating hormone)

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31
Q

Hypothalamic-pituitary-testicular axis:
what does LH from anterior pituitary act on

A

LEYDIG CELLS in TESTICLES

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32
Q

Hypothalamic-pituitary-testicular axis:
what do LEYDIG CELLS in testicles SECRETE in response to LH

A

ANDROGENS

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33
Q

Hypothalamic-pituitary-testicular axis:
effects of ANDROGENS (4)

A
  • 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
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34
Q

Hypothalamic-pituitary-testicular axis:
what does FSH from the anterior pituitary act on

A

SERTOLI CELLS
‘nurse cells’
- nurse GROWTH and NURTURE of SPERMATAZOA

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35
Q

Hypothalamic-pituitary-testicular axis:
EFFECTS of SERTOLI CELLS

A
  • AROMATISED into ESTROGENS by aromatase
  • produce ANDROGEN-BINDING PROTEINS
  • SPERMATOGENESIS
  • NEGATIVE FEEDBACK EFFECTS in FSH - SECRETE INHIBINS
36
Q

Hypothalamic-pituitary-testicular axis:
what do ANDROGEN BINDING PROTEINS do (from sertoli cells)

A

maintain conc. of testosterone in testicles

important for development of sperm (spermatogenesis)

37
Q

What is a TESTICLE made up of

A

TESTICULAR LOBULES

38
Q

what are TESTICULAR LOBULES of testes composed of

A

SEMNIFEROUS TUBULES

39
Q

what cells are inside SEMNIFEROUS TUBULES

A

SERTOLI CELLS (nurse development of sperm between them)

40
Q

what cells are found between SEMNIFEROUS TUBULES in INTERSTITION

A

LEYDIG CELLS (testoserone)

41
Q

where is the PREDOMINANT PRODUCTION of ESTROGENS

A

in OVARIES by GRANULOSA CELLS

also produced locally in tissues

42
Q

in which CELLS in the OVARIES is ESTROGEN produced

A

GRANULOSA CELLS

43
Q

ESTRADIOL can also be PRODUCED by..

A

CONVERSION of circulating ANDROGENS by AROMATISATION

44
Q

ESTROGEN SECRETION is under the influence of which hormones

A

LH and FSH
- GONADOTROPINS from anterior pituitary

45
Q

FUNCTIONS of ESTROGEN (6)

A

*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

46
Q

Hypothalamic-pituitary-ovarian axis (women):
role of HYPOTHALAMUS

A

release GnRH (GONADOTROPIN RELEASING HORMONE) to anterior pituitaary

47
Q

Hypothalamic-pituitary-ovarian axis (women):
role of HYPOTHALAMUS

A

release GnRH (GONADOTROPIN RELEASING HORMONE) to anterior pituitary

48
Q

Hypothalamic-pituitary-ovarian axis (women):
response of ANTERIOR PITUITARY to GnRH from hypothalamus

A

secretes LH and FSH

49
Q

Hypothalamic-pituitary-ovarian axis (women):
what does LH from anterior pituitary act on

A

THECA CELLS (in ovarian follicle)

50
Q

Hypothalamic-pituitary-ovarian axis (women):
what does FSH act on

A

GRANULOSA CELLS

51
Q

Hypothalamic-pituitary-ovarian axis (women):
what do THECA CELLS SECRETE in response to LH (2)

A

ANDROGENS (act on granulosa cells)
PROGESTINS (progesterone-like hormones)

52
Q

Hypothalamic-pituitary-ovarian axis (women):
what do GRANULOSA CELLS SECRETE in response to FSH (4)

A
  • ESTROGENS
  • add to PROGESTINS
  • INHIBINS (negative feedback)
  • ACTIVINS
53
Q

what is ESTROGEN responsible for in MENSTRUAL CYCLE

A

OVULATION

54
Q

what in the OVARY, MATURES, RUPTURES and DISCARCHES OOCYTE

A

GRAAFIAN FOLLICLE

55
Q

what organ is formed in OVARY after RUPTURE

A

CORPUS LUTEUM (secretes progesterone)

56
Q

what does the CORPUS LUTEUM become if no pregnancy

A

CORPUS ALBICANS

57
Q

parts of FALLOPIAN TUBE

A
  • Fimbriae (finger like)
  • Infundibulum
  • Ampulla
  • Isthmus
58
Q

what is the MAIN PROGESTIN

A

PROGESTERONE

59
Q

what is PROGESTERONE secreted by

A

CORPUS LUTEUM (formed by ovary after ovulation)

60
Q

PROGESTERONE is a pro… hormone

A

pro PREGANCY

61
Q

FUNCTIONS of PROGESTERONE (7)

A

*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

62
Q

how does PROGESTERONE prevent fertilisation by further sperm

A

INCREASES VISCOSITY of CERVICAL MUCUS

63
Q

MENSTRUAL CYCLE varies between how many days

A

28-35 DAYS

64
Q

when does FOLLICULAR / PROLIFERATIVE PHASE begin (when an egg matures in ovaries)

A

with the BEGINNING of MENSES

65
Q

how long does FOLLICULAR / PROLIFERATIVE PHASE last

A

14-21 DAYS

66
Q

role of FSH in MENSTRUAL CYCLE (4)

A
  • FOLLOCULAR RECRUITMENT
  • FOLLICULAR GROWTH
  • INCREASED ESTROGEN SECRETION
  • appearance of LH RECEPTORS on GRANULOSA CELLS in preparation for LH SURGE
67
Q

what are the 2 PHASES of the MENSTRUAL CYCLE

A

FOLLICULAR PHASE
LUTEAL PHASE

68
Q

how long is the LUTEAL PHASE OF MENSTRUAL CYCLE

A

14 DAYS (constant)

69
Q

what are the EFFECTS of ESTROGEN in the 2 PHASES

A

FOLLICULAR: STIMULATORY effect
- stimulates LH SURGE
- stimulates slight FSH SURGE

LUTEAL: INHIBITORY effect
- INHIBITS LH & FSH (therefore remain flat)

70
Q

what happens in FOLLICULAR PHASE (before ovulation) in terms of HORMONE levels

A
  • FSH INCREASE
    (developmet of follicles and granulosa cells make estrogen)
  • ESTROGEN INCREASE & PEAK
    stimulates
  • LH SURGE
  • slight FSH surge
71
Q

what is the LH SURGE ESSENTIAL for

A

RELEASE OF OVUM
- usually happens 36 hours after the surge

FORMATION or CORPUS LUTEUM

72
Q

what is OVULATION TRIGGERED BY

A

RAPID RISE in ESTRADIOL LEVEL

positive feedback of
oestradiol at pituitary & hypothalamus results
in the LH surge

73
Q

how are HORMONE LEVELS in LUTEAL PHASE of menstrual cycle

A
  • PROGESTERONE LEVELS INCREASE
  • ESTROGEN levels INCREASE again (secreted by Corpus Luteum)
  • LH & FSH FLAT (inhibited by estrogen)
74
Q

what is ESTROGEN SECRETED from in LUTEAL PHASE

A

CORPUS LUTEUM

75
Q

LH PULSE FREQUENCY in FOLLICULAR PHASE opposed to in Luteal Phase

A

EVERY 90 MINUTES

( every 4 HOURS in luteal phase)

76
Q

if PREGNANCY occurs then CORPUS LUTEUM is maintained by..

A

HCG secreted by TROPHOBLAST (placenta)

77
Q

if no pregnancy, CORPUS LUTEUM DEGENERATED into… by…

A

CORPUS ALBICANS
by a process called LUTEOLYSIS

78
Q

AROMATASE is an important enzyme in which pathway

A

STEROIDOGENESIS PATHWAY

79
Q

AROMATASE is responsible for which 2 CONVERSIONS in peripheral tissues

A
  • ANDROSTENEDIONE to ESTRONE
  • TESTOSTERONE to ESTRADIOL
80
Q

ANDROSTENEDIONE is converted to what by AROMATASE

A

ESTRONE

81
Q

TESTOSTERONE is converted to what by AROMATASE

A

ESTRADIOL

82
Q

AROMATASE is present in several tissues such as… (7)

A

GONADS
VASCULAR ENDOTHELIUM
ENDOMETRIUM
SKIN
BONE
BRAIN
ADIPOSE TISSUE
PLACENTA

83
Q

AROMATASE DEFICIENCY (due to mutations in CYP19A1) can result in..

A

OVERPRODUCTION of TESTOSTERONE
& deficiency of estrogens

females affected by this are born with ambiguous genitalia

84
Q

what is HYPOGONADISM

A

INABILITY of the TESTICLES / OVARIES to
PRODUCE TESTROSTERONE or ESTROGEN respectively

85
Q

what is PRIMARY HYPOGONADISM due to

A

DEFECT at the level of the GONAD
i.e. the TESTICLES or the OVARIES

86
Q

what is SECONDARY HYPOGONADISM due to

A

DEFECT at the level of the PITUITARY or HYPOTHALAMUS
- causing REDUCED amplitude or pulsatility of
FSH, LH or GnRH SECRETION

ENDOCRINOLOGY (11 decks)

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