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Human Physiology 1 > Reproduction Lectures 2021 - THE ENDOCRINOLOGY OF REPRODUCTION > Flashcards

Reproduction Lectures 2021 - THE ENDOCRINOLOGY OF REPRODUCTION Flashcards

1
Q

The brain controls…

A

reproduction (through GnRH)

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2
Q

GnRH containing neurons mainly located in the…

A

ARCUATE nucleus within the hypothalamus

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3
Q

Posterior pituitary

A

extension of Hypothalamus with the SON & PVN neurons extending down into the posterior pituitary

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4
Q

Anterior pituitary

A

governed by hormones released from hypothalamus into the portal blood supply (“Hypothalamic-hypophysial portal system”)
- the ARCUATE NUCLEI that will be in the hypothalamus synapse with the neurohemal area known as the MEDIAN EMINENCE, & the contents of those neurons that are dumped into the portal blood supply flow down into the anterior pituitary & in the context of GnRH - will target the GONADOTROPHS (will ultimately syn. & release LH & FSH)

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5
Q

Gonadotrophin Releasing Hormone (GnRH) is known as the…

A

master sex hormone

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6
Q

Originally, for GnRH thought that…

A

2 hormones were involved LHRH & FSHRH

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7
Q

In the absence of GnRH…

A

you won’t get:

  • syn. & release of LH & FSH
  • syn. & promototion of sex steroid production from the gonads in either males or females
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8
Q

Concentration of GnRH in the circulation is…

A

really LOW & practically undetectable

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9
Q

Where will you find GnRH in abundance?

A

sample blood from the portal blood supply

- v. HIGH concen. within the portal blood supply

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10
Q

GnRH as a molecule (Pre-pro GnRH)

A

Pre-pro GnRH:

Signal peptide - 23 AA’s

Mature peptide - 10 AA’s

3aa

GnRH-associated peptide (GAP) - 56 AA’s

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11
Q

Which peptide is the bioactive peptide?

A

mature peptide

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12
Q

Tonic pulses in both sexes every…

A

1-3h

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13
Q

Tonic pulses of GnRH are critical for…

A

normal function & release of FSH & LH

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14
Q

GnRH pulse generator influences…

A

syn. & release of FSH & LH

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15
Q

Continued administration of GnRH will..

A

inhibit FSH & LH release - downregulation of GnRH signalling pathway

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16
Q

Diff. mech’s proposed for pulse generation:

A
  1. Threshold of release & autocrine regulation

2. Stimulation via NE & local inhibition via Dopamine or GABA (universal inhibitor for neural function)

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17
Q

What was studied mostly in rats & mice (mammalian studies)?

A

if you elevate levels of GnRH, you’ll ultimately inhibit FSH & LH levels
- so if you maintain really high levels all the time, you’ll get an inhibition of those peptide hormones

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18
Q

GnRH with a nerve cell

A

GnRH released & will act on itself to promote release of GnRH, but once that threshold is hit, then you start to get a reversal of that autocrine regulation & it shuts off (sort of self-regulating feedback control)
- if that is based on that threshold you’ll get pulses of GnRH release as more is released

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19
Q

Kisspeptin

A

imp. hormone that will promote GnRH release

regulated by estrodial (E2) which also promotes kisspeptin release depending on the circulating concen. of estrodial

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20
Q

High plasma estrogen (females)

A

+ feedback on GnRH –> ↑ GnRH –> ↑ FSH & LH –> Ovary –> Ovulation

+ feedback setpoint

  • estrogens will target kisspeptin which will promote ↑ GnRH from the arcuate nuclei
  • might get further ↑E2
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21
Q

Moderate plasma estrogen (females) or androgen (males)

A
  • feedback on GnRH –> ↓ GnRH –> ↓ FSH & LH –> Gonad –> ↓ estrogen or ↓ androgen
  • feedback setpoint
  • classic/normal in males
  • still androgens being produced but it acts as a (-) feedback regulation, so you won’t get v. high plasma levels of androgens in the same way as you get v. high levels of estrogens within females
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22
Q

Low plasma estrogen (females) or androgen (males)

A

no feedback on GnRH –> ↑ GnRH –> ↑ FSH & LH –> Gonad –> ↑ estrogen or ↑ androgen

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23
Q

In males, prepubertal period LH and FSH are…

A

not secreted

GnRH secretion begins slowly at the onset of puberty

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24
Q

What sets the wheels in motion (in terms of puberty)?

A

hard to know exactly

  1. Energy requirement
  2. Genetic basis in timing to this
  3. Melatonin (linked to HPG axis)
    - varies depending on season
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25
Q

Describe GnRH in males

A

Hypothalamus –> +ve to FSH & LH

FSH –> +ve to Sertoli cells –> +ve to spermatogenesis, ABP, Inhibin

Inhibin –> -ve to FSH

LH –> +ve to Leydig cells –> testosterone –> +ve to Sertoli cells & -ve to hypothalamus (close GnRH prod. & inhibit both FSH & LH release from ant. pituitary)

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26
Q

FSH target cells involved in…

A

gamete syn.

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27
Q

LH target cells involved in…

A

steroid syn.

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28
Q

Inhibin

A

selectively (-)ly feedsback on FSH in partic. & will limit prod. of FSH from ant. pituitary

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29
Q

ABP

A

imp. within the seminiferous tubule, so it can bind testosterone & also it is released in the blood

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30
Q

Spermatogenesis

A

all things related to dev. of sperm

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31
Q

Teritary follicle has…

A

cell types with major source of Estrogens

32
Q

Corpus luteum produces…

A

estrogens & progesterones

33
Q

Where do we get a shift in steroidogenesis?

A

as the cells in the follicle transform to luteal cells

34
Q

Steroidogenesis in the follicle

A

page 77

delta5 = dominant pathway in thecal & granulosa cells

delta4 = dominant pathway in luteal cells

progesterone - imp. for maintenance of pregnancy & is a major product from corpus luteum
- becomes 1 of the major products as it shifts from delta5 to delta4

35
Q

2/3 cell model of ovarian steroidogenesis

A

page 78

3 cells = thecal, granulosa, & luteal

estradiol is the primary end product but estrone & estriol is also produced

FSH primary target is aromatase

36
Q

LH

A

imp. for promoting androgen production in thecal cells, therefore increase LH so does androgen produc.

37
Q

FSH

A

imp. for promoting conversion of those androgens to estrogens in the granulosa cells

38
Q

Only need ____ amount of FSH to promote aromatase activity

A

small

- FSH doesn’t have to increase dramatically to promote aromatase activity

39
Q

Major driving force for promoting increases in circulating levels of estrogens that are derived from thecal & granulosa cells is…

A

LH & the production of the substrate (andro’s convert to estrogens)

40
Q

Hormonal control of the Ovarian cycle

Unlike males because:

A
  1. Cyclical in nature (increases/decreases of sex steroids that happen in a predictable & timely way)
  2. FSH and LH do not specifically target gametogenesis or gonadal hormones respectively (but do play role in that)
  3. There are both –ve and +ve feedback controls
41
Q

Why do we always use follicular phase?

A

b/c it’s timed with menses which is an obvi. starting point to use

42
Q

FSH is…

A

high over the 1st ~7 days

- promoting dev. of stimulating follicular dev. in ovary

43
Q

Ovulation

A

egg released form follicle into fallopian tube

44
Q

LH surge at ovulation b/c & why is that imp.?

A

inhibin has been used to selectively inhibit too much FSH release

imp. b/c if you have a maintained heightened level of FSH, you will start to promote additional follicular dev. & you don’t want that at this stage b/c you already selected a follicle to go further for maturation & ovulation so you don’t want additional follicles to be promoted for maturation & ovulation at this time to limit follicular dev. of additional follicles

decrease in FSH is due to inhibin (-) feedback reg.

45
Q

Surge in LH causes:

A
  1. DEcrease in estrogens (based on (+) feedback role of E’s, inhibition of E prod. now ends up in (-) feedback reg. of GnRH, so decline of LH syn. & release)
  2. REinitiate miotic division with the oocyte
  3. INcrease prostaglandins (PG’s) production (aid in rupturing of follicle & release of egg in fallopian tube)
  4. INcrease –> follicle –> luteal (promotion of differentiation)
46
Q

Decline in FSH leads to…

A

atresia (degredation of all but the leading follicle)

47
Q

In follicular phase we see increase…

A

estrogen production & dev. of antral space

48
Q

As follicle grow, we get…

A

more estrogen prod. - driven by actions of LH as it starts to increase

49
Q

In luteal phase we get…

A

increase in progesterone’s

50
Q

Low levels of FSH can still…

A

maintain that aromatase activity (to fuel rise in estrogens during follicular phase)

51
Q

As inhibin starts to rise, we get…

A

a selective inhibition of FSH from ant. pituitary

52
Q

Anti Mullerian Hormone (AMN)

A

secreted by the larger follicle

  • is involved in deciding which follicle moves further for maturation
  • may also inhibit maturation of neighbouring follicles (meaning that single follicle goes forward for maturation & the dev. of neighbouring ones are inhibited)
53
Q

Ovarian follicle secretes…

A

estrogen

↑ in size → ↑ in estrogens

54
Q

During the luteal phase, LH will…

A

maintain prod. of P’s & E’s within the corpus luteum through promotion of the P450 SCC

55
Q

Decrease in FSH/LH in luteal phase is due to…

A

differentiation of follicular cells to luteal cells & start to see increase in progesterone & P is a key inhibitor of LH & FSH

56
Q

We see an increase in progesterone in the luteal phase that is…

A

quickly as follicular cells differentiated in luteal cells (quick b/c of change in steroidogenetic pathway - not in delta5 pathway)

57
Q

Surge in LH in ovulation…

A

terminated the follicular phase & initiates the luteal phase

58
Q

Once we get to mature corpus luteum…

A

increase in E’s

increase in inhibin for selective inhibition of FSH b/c don’t want another follicle dev. now

increase in P’s

59
Q

Secretory phase

A

within endometrium lining which is critical for implantation of the blastocyst in preparing for pregnancy

60
Q

The surge in LH is a critical point & is…

A

regulated by +ve feedback

61
Q

In proliferation phase…

A

hyperplasia of endometrium lining

62
Q

Progesterone stimulates exocrine activity to…

A

increase embryotroph (nutrient rich fluid-uterine milk to support early dev. of blastocyst & subsequent embryogenesis)

63
Q

In the late follicular phase & ovulation…

A

(+) feedback for short amount of time & then to (-) for the cause of the decrease of LH & FSH

64
Q

Placental hormones

A
  • Human Chorionic gonadotropin (hCG) - glycoprotein belonging to FSH/LH fam (2 subunits a & B)
  • Human Placental Lactogen (chorionic sommatomammotropin)
65
Q

Human Chorionic gonadotropin (hCG):

A

– Produced by the blastocyst to preserve the corpus luteum. NB: progesterone will inhibit LH release

66
Q

Human Placental Lactogen (chorionic sommatomammotropin):

A

– Involved with mammary gland development (although not essential) also involved with regulating maternal metabolism
- linked with gestational diabetes

67
Q

Gestational diabetes

A

classic pair-offspring conflict

  • child wrestling with mother for nutrients & control of those nutrients
  • females may suffer during gesta.
  • ~90% of cases once child born, symptoms disappear
  • not uncommon
  • normally doesn’t continue but can as diabetes
68
Q

Human Chorionic gonadotropin (hCG)…

A

declines over time as the E’s & P’s in the circulation in the female carrying that child increase over time

69
Q

At delivery…

A

dramatic decline in all 3 hormones (hCG, E & P)

- more of a ratio of E & P than just E that are a good sign of parturition about to happen

70
Q

Triggers for onset of parturition

A

page 84-85!!

all v. strong (+) feedback reg that promotes parturition all set off by dev. of fetal lungs & interaction b/t CRH & ACTH

71
Q

Interleuhin IB (IL-1B)

A

local agent that’ll target specific cell types & various diff. pathways

72
Q

Myometrial cells

A

muscle cells that line the uterus

73
Q

Role of PG’s in parturition:

A

cervical stretching & promoting contraction within the endometrial lining

74
Q

“Let down” reflex in nursing mothers

A

inhibition of PIH (prolactin inhibiting hormone - Dopamine) secretion (from hypothalamus) allows the stimulus of milk production by PRL

(+) feedback reg.

75
Q

If female is under prolonged stress, i.e. elevated levels of cortisol, they will tend to…

A

deliver before term

76
Q

If female has normal levels of cortisol, you can…

A

predict when that individual will give birth pretty closely

77
Q

If female has v. low levels of cortisol, gestation tends to…

A

go longer

Human Physiology 1 (32 decks)

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