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MBCHB3: Reproduction, Development and Ageing > Lecture 1: Reproductive Endocrinology > Flashcards

Lecture 1: Reproductive Endocrinology Flashcards

1
Q

What are the features of hormone systems in a general overview?

A
  • > Released from a set of cells, have tissue and receptor specificity
  • > Hierarchical arrangement
  • > Amplification
  • > Homeostatic mechanisms involving negative and positive feedback loops regulating hormone levels
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2
Q

What are the three main classes of hormones:

A
  • Lipids
  • Proteins
  • Monoamines
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3
Q

Write some notes on lipid hormones as a class

A
  • Two main subtypes:
  • > Steroids; i.e progesterone, androgens, estrogens, corticosteroids
  • > Eicosanoids: Prostaglandins, leukotrienes

Steroids produced in the gonads (not sure entirely true…)

HYDROPHOBIC, Lipophilic

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4
Q

Write some notes on protein hormones as a class:

A

Five main subtypes:

  • Gonadotrophic glycoproteins (FSH, LH, hCG)
  • Somatomammotrophic (prolactin)
  • Cyotkines
  • Small peptides i.e GnRH, Oxytocin

FSH, LH and Oxytocin made in pituitary

Water soluble

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5
Q

Write some notes on monoamines as a class of hormone

A

Catecholamines

Found in neurons

Water soluble

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6
Q

What are the androgens?

A

Androgens =

Testosterone (mainly produced by testis and is associated with development and maintenance of male characteristics and fertility)

5a dihydrotestosterone

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7
Q

What are the oestrogens?

A

Oestrogens = Ovary

Oestradiol, Oestrone, Oestriol

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8
Q

What are the progestagens?

A

Progestagens: Ovary, placenta

i.e progesterone

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9
Q

Describe the structure of steroid hormones:

A
  • All derived from sterol precursor: Cholesterol

- The ‘steroids’ are compounds containing the perhydrocyclopentenophenanthrene nucleus

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10
Q

What is the rate limiting step in steroid biosynthesis?

A

The conversion of Cholesterol to pregnenolone (regulated by LH)

All steroids are related in the synthesis tree i.e

  • Cortisol and aldosterone are corticosteroids.
  • Progestagens, androgens and oestrogens are all linked.
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11
Q

What converts testosterone to dihydrotestosterone?

A

5a reductase

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12
Q

Can androgens be produced elsewhere from the testis?

A

Can also be produced by extraglandular tissues (mainly adipose tissues) from circulating androstenedione (more significant in women)

Normal testosterone levels:
Males: 11-40nmol/L
Females: 0.5-2.5nmol/L

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13
Q

What is the function of 5adihydrotestosterone?

A
  • 5aDHT is more potent than testosterone

- Principle androgen in a number of target tissues i.e male accessory sex glands, skin, tissues of external genetalia

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14
Q

Where is 5aDHT made?

A
  • Some in testes, mainly arises from local production in target tissue via 5a reductase on circulating testosterone
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15
Q

What is the function of finasteride?

A

FInasteride (Propecia), inhibits 5aDHT, and has been used in treatment of benign prostatic hyperplasia, hirsuitism and preventing male pattern hair loss (curious because testosterone stimulates hair growth)

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16
Q

What are the relative potencies of androgens?

A

5aDHT: 100%
Testosterone:50%
Androstenedione: 8%
Dehydroepiandrosterone (DHEA): 4%

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17
Q

What do androgens do?

A
  • Induce and maintain differentiation of male tissues
  • Induce and maintain some secondary sex characteristics of males and body hair of females
  • Induce and maintain some secondary sexy characters of males (Accessory sex organs)
  • Support spermatogenesis
  • Influence sexual and aggressive behaviour
  • Promote protein anabolism, somatic growth and ossification
  • Testosterone regulates secretion of gonadotrophins via negative feedback
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18
Q

What is the role of estrogens?

A

Main role is in development and maintenance of female characteristics and fertility

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19
Q

What are normal estradiol levels?

A

Normal females: 200-1100pmol/L (cycle dependant)
Post menopausal: <110 pmol/L
Adult males: <160pmol/L

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20
Q

What is the main site of oestrogens production?

A

Oestradiol: Granulosa cells of the growing follicle (non-pregnant of reproductive age). Post ovulation the corpus luteum produces a small amount of estradiol

Adipose tissue converts a small amount of androstenedione and testosterone into oestrone (males and post meno women)

Oestriol is produced by the placenta from DHEAS

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21
Q

Insert picture of slide 15. Cycle and hormones

A

now please

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22
Q

What are the relative potencies of the estrogens?

A

Oestradiol (100%)
Oestriol (10%)
Oestrone (1%)

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23
Q

What is the function of estrogens?

A
  • Stimulate secondary sex characteristics of females
  • Endometrial growth (proliferative phase)
  • Prepare endometrium for progestogen action
  • Stimulates the cervix to secrete mucous
  • Stimulates growth and activity of the mammary gland
  • Stimulates proliferation of vaginal epithelial cells
  • Mildly anabolic (calcification)
  • Active during pregnancy
  • Regulates the secretion of ganadotrophins
  • Associated with sexual behaviour in some species
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24
Q

What is progesterone?

A

The major steroidal hormone of the corpus luteum and of the palcenta

25
Q

What does progesterone do?

A

Prepares the reproductive tract for implantation and the maintenance of pregnancy

26
Q

Is progesterone found from other sources?

A

Outside of the postovulatory phase of the menstural cycle and of pregnancy, only small amounts of progesterone (mainly from adrenal cortex) are present in ciruclation.

27
Q

What are the relative progesterone levels during the MC?

A

Pre-ovulation: < 4 nmol/L
LH surge: < 4-10 nmol/L
Post-Ovulation (mid luteal phase: 25-120 nmol/L

28
Q

What is the function of progesterone?

A
  • Reduces mitotic proliferation of the endometrium
  • Promotes a secretory endometrium with an increased water content
  • Maintains the uterus during pregnancy
  • Inhibits cervical mucus secretion
  • Stimulates the growth of mammary glands, but suppress secretion of milk
  • Regulates the secretion of gonadotrophins
  • General mild catabolic effect / CNS and thermoregulation - elevates the basal body temperature
29
Q

Describe steroid hormone transport:

A
  • Low levels of free steroid
  • Bind to carrier proteins or chemically modified to increase their solubility in plasma
  • Most bound to albumin, and specific proteins i.e sex hromone binding globulin (SHBG) and cortisol binding globulin (CBG) aka transcortin
  • > Bioavailability of sex hormones is regulated by SHBG
  • > Bound hormones are in equilibrium with free hormone (free can diffuse quicker into tissues)
30
Q

Why is the proportion of bound:unbound important clinically?

A

Free is more readily active and actionabale.

31
Q

What are the two types of hormone receptors and how do they differ?

A 
Cell Surface receptors: 
i.e LH, FSH
-> Hydrophilic
-> No transport of proteins
-> Short half life
Mediator: cAMP, Ca2+
Intracellular receptors
i.e Oestrogen, Progesterone, Testosterone
-> Hydrophobic
-> Transport of proteins
-> Long half life
Mediator: Receptor Hormone Complex
32
Q

How is the action of the hypothalamus mediated?

A

Homeostatic regulator

Mediated by pulsatile release of hypothalamic hormones

33
Q

Write some notes on the anterior pituitary:

A
  • Produces its own hormones, but, their release is controlled by the hypothalamus.
  • Linked to hypothalamus via vascular route
  • Consists of a collection of cell types, each of which respond to specific stimuli and release specific hormones into the systemic circulation.

i.e FSH, LH and GH

34
Q

Write some notes on the posterior pituitary:

A
  • Stores hormones which are synthesised in the hypothalamus. (Paraventricular and supraoptic nuclei in hypothalamus) (Neurosecretory neurons)
  • Linked to hypothalamus by direct neuronal connections
  • Made up of glial tissues and axonal termini

i.e Oxytocin and ADH

35
Q

Describe how the neurosecretory neurons are able to function:

A

The neurosecretory peptide hormones, synthesised in the hypothalamus are bound to carrier proteins and pass down to the axon terminals, where they are stored as secretory vesicles.

36
Q

Whats the difference between ADH and Oxytocin?

A

One amino acid difference between these two hormones which have vaastly differing functions

37
Q

What is the function of Oxytocin released from the post. pituitary?

A

Oxytocin has major effects on smooth muscle contraction

  • Milk ejection
  • Contraction of the uterus during childbirth
  • Sexual attraction
38
Q

What is the role of ADH?

A

Water retention and vasoconstriction

39
Q

What name is synonymous with ant. pituitary?

A

Adenohypophysis

40
Q

Describe how the anterior pituitary works:

A

Neurosecretory neurones synthesise releasing and inhibiting hormones in their cell body into vesicles, which travel to the axonal terminus

In response to nerve impulses, these neurosecretory peptide hormones are secreted into the hypophyseal portal system

41
Q

Describe the hypophyseal portal system:

A

Sup. hypophyseal arteries branch off the internal carotid. These form the primary cap. plexus of the median eminence (hyopthalamus).

These send descending hypophyseal portal veins, these form capillaries in the neurohypohysis. These also recieve inferior hypophyseal arteries from the internal carotid. From these plexus. Inferior hypophysial veins drain into the cavernus sinus

42
Q

What are the hypothalamic hormones that act on the ant. pituitary?

A

GnRH -> LH and FSH
CRH (Corticotrophin releasing hormone) -> ACTH
GHRH -> GH
GHIH (inhibits) GH

PRH -> Prolactin
TRH (Thyrotropin) -> Prolactin and TSH
PIH (inhibts) prolactin (aka dopamine)

43
Q

What are the types of anterior pituitary secretory cells?

A

Acidophil: GH or Prolactin
Basophil: TSH, ACTH, FSH or LH

44
Q

Insert picture of feedback loops

A

Slide 35

45
Q

Describe the release of GnRH and why it occurs like that:

A

GnRH secretion is pulsatile (60-90min)

  • Prevents receptor sensitisation or down regulation
  • Correspondingly pituitary hormones exhibit pulsatile release
46
Q

What is the pulse interval and amplitude of GnRH regulated by?

A
  • Ovarian steroid hormones esp. estradiol
  • Neural influences
  • Endogenously produced brain opioids, i.e endorphins
  • Gonadotrophins themselves
47
Q

Write some notes on the tertiary structure of gonadotrophins and what is its implication

A
  • Alpha and beta subunits
  • Alpha subunit is common and confers specific specificity
  • Beta unit confers hormonal specificity
48
Q

Where in general do FSH and LH bind and what do they do?

A

Bind to receptors in the ovary and testis

Promote the synthesis of sex steroid hormones and gametogensis

FSH: Growth of ovarian follicles and spermatozoan
LH: Secretion of gemale sex hormones and stimulates ovulation. Stimulates production of testosterone

49
Q

Describe the LH and FSH loop in males:

A

Hypothalamus via GnRH stimulate pituitary to release LH and FSH. = Testosterone and spermatogenesis from the testis. Testosterone inhibits at the level of the pituitary via inhibin and directly inhibits the hypothalamus

50
Q

Describe the LH and FSH loop in Females:

A

Hypothalamus via GnRH stimulate pituitary to release LH and FSH. = Follicle growth and ovulation. Estradiol negatively feedbacks to the pituitary via inhibin and the hypothalamus via progesterone.

51
Q

What are GnRH anaolgues important in the treatment for?

A
  • Endometriosis, fibroids, breast cancer and menorrhagia
  • Precocious puberty
  • Benign prostatic hyperplasia
  • IVF therapy
52
Q

What is the consideration for GnRH anaolgues?

A

GnRH anaolgues over prolonged periods can cause pituitary FSH and LH oversecretion. Followed by down regulation/desensitisation of GnRH receptors.

53
Q

Describe the growth hormone feedback loop

A

Hypothalamus releases GHRH which causes GH release. GH causes IGF-1 release from liver. This causes a wide range of cell growth in various tissues. IGF-1 negative feedback loop to the pituitary and causes somatostatin release.

Somatostatin inhibits GH release.

54
Q

What is acromeagly?

A
  • Excessive GH and thus IGF-1 release = Resulting in enlarged facial features, hands, feet.
  • Very gradual onset

Arises from: GH secreting pituitary tumor (usually benign)
- GHRH hypothalamic tumor.

55
Q

What are the treatments for acromeagly?

A
  • Somatostatin analogues
  • GH receptor antagonists
  • Surgical removal or reduction in tumor
56
Q

Describe the thyroid endocrine pathway:

A

Hypothalamus -> TRH -> Pituitary -> TSH, which acts on thyroid to release T3,4

(T3,4 controls how the body uses energy, makes proteins, controls how sensitive the body is to other hormones)

T3,4 negatively feedback to pituitary and hypothalamus. AS well as stimulating somatostatin release which inhibits the pituitary

57
Q

Describe how iodine deficiency results in goiter

A

Iodine deficiency prevents the thyroid making T3 and T4. This reduces negative feedback resulting in higher TRH and TSH levels and eventually thyroid hyperplasia.

58
Q

Describe hashimotos thyroiditis:

A

Hypo thyroidism

  • High TSH, low T4
  • Treated with thyroid hormone pills
59
Q

Describe Graves disease:

A

Hyperthyroidism

  • Overproduction of T4, enhanced negative feedback and a reduction in TSH
  • Treated by radioactive iodine (reduce thyroid size), methimazole (reduce T4 production)

MBCHB3: Reproduction, Development and Ageing (24 decks)

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