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Advanced concepts in reproduction > Week 1 > Flashcards

Week 1 Flashcards

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1
Q

How do endocrine substances (hormones) work?

A

Secreted directly into the blood stream - transported to distant target tissue to exert its actions

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2
Q

How do paracrine hormones work?

A

Released by a gland cell and diffuses through the extracellular space to its target cell within the same gland

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3
Q

How does an autocrine hormone work?

A

Released by a cell - exerts its actions on the same cell

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4
Q

What is neuroendocrine?

A

A neuronal hormone released into a synaptic cleft adjacent to where the neurone contacts the target cell.

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5
Q

How many types of hormones are there from a chemical standpoint?

A

Four

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6
Q

What are the 4 main groups of hormones?

A
  • Protein and peptide hormones e.g. insulin, luteinising hormone
  • Steroid hormones e.g. cortisol, oestradiol
  • Hormones derived from tyrosine e.g. thyroxine and norepinephrine
  • Eicosanoids e.g. prostaglandins and leukotrienes
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7
Q

What are protein and peptide hormones?

A

Hormones synthesised from amino acids

Vary in size - peptides are very small and consist of only a single chain of amino acids
E.g. Thyrotropin releasing hormone (TRH) consists of only 3 amino acid (aa) residues. Gonadotropin releasing hormone (GnRH) consists of 10aa

Stored in secretory vesicles until needed

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8
Q

What are glycoprotein peptide hormones?

A

Glycoprotein hormones are large molecules

Gonadotrophins (luteinising hormone, LH; Follicle stimulating hormone, FSH; and human chorionic gonadotrophin, hCG) consist of two distinct peptide chains (called alpha and beta subunits) which are linked together by non-covalent bonds

The alpha subunit is common to LH, FSH, hCG and Thyroid stimulating hormone (TSH); biological specificity is conferred by the beta subunit

Varying degrees of glycosylation

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9
Q

What is the method of action of protein/peptide hormones?

A

Hydrophilic

Bind to cell surface receptors (e.g. GPCRs, enzyme linked receptors)

Initiate downstream signalling pathways that mediate biological effects

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10
Q

What are steroid hormones?

A

The steroids are a large class of lipids which are synthesised mainly in the adrenal cortex, testis, ovary and placenta from a common precursor, cholesterol

They all have a common ring structure which consists of 3 six-membered rings and 1 five-membered ring

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11
Q

What is the method of action of steroid hormones?

A

Hydrophobic
- Transported in the blood stream bound to carrier proteins
- Can pass through the cell membrane

Bind to receptors in the cytoplasm

These receptors are sequestered to the cytoplasm bound to chaperone proteins (heat shock proteins)

Upon ligand binding, they dissociate from the chaperone proteins and translocate to the nucleus

In the nucleus, they form homodimers and bind to DNA response elements that consist of two inverted repeats

Also, alternative signalling pathways including non genomic action

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12
Q

What are the hormones derived from tyrosine? What do they bind to?

A

Include adrenaline, noradrenaline, dopamine and the thyroid hormones thyroxine (T4) and triiodothyronine (T3)

All bind to cell surface receptors

Noradrenaline, dopamine and adrenaline bind to cell surface receptors (GPCRs)

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13
Q

What are the method of actions of these hormones derived from tyrosine?

a. Adrenaline, noradrenaline and dopamine

b. Thyroxine (T4) and Triiodothyronine (T3)

A

a. Adrenaline, noradrenaline and dopamine are hydrophilic

They bind to cell surface receptors (GPCRs)

b. Thyroid hormones thyroxine (T4) and triiodothyronine (T3) are hydrophobic

They enter cells (via transporter proteins) and bind to nuclear receptors

Cannot cross plasma membrane freely (goes against theory about hydrophobic molecules)

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14
Q

What are hormones derived from fatty acids?

A

Eicosanoids

Two major classes of messengers
- prostaglandins (PGs)
- leukotrienes (LTs)

Derived from arachidonic acid (AA)

Short half-life –> act near the site of synthesis

They bind to GPCRs on target cells

PGs are formed in most tissues of the body:

  • The type of PG formed varies depending on the type of downstream enzymes present
  • Produced in uterus - role in embryo implantation; and in foetal membranes - role in parturition
  • Found in seminal vesicles - promote sperm motility
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15
Q

How are hormones transported in the blood?

a. Peptide hormones
i.e FSH, LH

b. Amino acid-derived hormones

i. Catecholamines (i.e. adrenaline, noradrenaline, dopamine)
ii. Thyroid hormones

c. Steroids
i.e. Estradiol, progesterone, testosterone

A

a.
Water soluble (hydrophilic)
Dissolve in the plasma

b. i.
Water soluble (hydrophilic)
Dissolve in the plasma

b. ii.
Not soluble in water (hydrophobic/lipophilic)
Circulate in the blood mainly bound to plasma carrier proteins (hormone binding proteins)

c.
Not soluble in water (hydrophobic/lipophilic)
Circulate in the blood mainly bound to plasma carrier proteins (hormone binding proteins)

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16
Q

What is the free hormone hypothesis?

A

Free Hormone + Binding Protein ⇌ Hormone-protein complex

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17
Q

What are the main hormones and their hormone binding protein?

A

Estradiol and testosterone
Sex hormone binding globulin (SHBG)

Glucocoticoids
Corticosteroid binding globulin (CBG)

Thyroid hormones
Thyroid binding globulin (TBG)
Transthyretin (TTR)

Non-selective
Albumin

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18
Q

Describe the endocrine axes:

A

Hypothalamus
(inhibiting hormone, releasing hormone)

Anterior Pituitary
(Trophic hormone)

Target organ

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19
Q

What is the hypothalamus?

A

The region of the brain in charge of homeostasis

Anatomy conserved across vertebrate species

Receives sensory input from the external (light, nociception, temperature, odoranta) and internal (blood pressure, blood osmolarity, hormone levels) environment

Integrates inputs and orchestrates coordinated responses

Controls release of hormones by the pituitary gland

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20
Q

What are hypothalamic hormones?

A

The hypothalamus secretes releasing and inhibitory hormones

Releasing hormones stimulate the secretion of hormones by the anterior pituitary (GnRH, GHRH, TRH, CRH)

Inhibitory hormones inhibit the secretion of hormones by the anterior pituitary (SS, DA)

With the exception of dopamine (DA), which is derived from tyrosine, all other hypothalamic hormones are peptides

They act by binding to specific G-protein-coupled receptors (GPCRs) on the anterior pituitary cells

Pulsatile secretion; constant secretion can lead to receptor desensitisation

They have a short half-life

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21
Q

What are the hypothalamic hormones and their structure, receptor type, signalling pathways and method of action?

A

a. GnRH, peptide (10 amino acids), GPCR, increases Ca2+, PLC, IP3, PKC, stimulates FSH and LH secretion

b. GHRH, peptide (44 amino acids), GPCR, Activation of adenylyl cyclase/cAMP, stimulates GH secretion

c. SS, peptide (14 amino acids), GPCR, inhibits cAMP production, inhibits GH secretion

d. TRH, peptide (3 amino acids), GPCR, increases PLC, stimulates TSH secretion

e. DA, Catecholamine, GPCR, multiple G proteins, inhibits prolactin secretion

f. CRH, peptide (41 amino acids), GPCR, Stimulates cAMP production, stimulates ACTH secretion

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22
Q

What are the main parts of the pituitary gland (Hypophysis)?

A

Anterior pituitary
- Pars tuberalis
- Pars intermedia
- Pars distails

Adenohypophysis (epithelial tissue)

Posterior pituitary
- Infundibular stalk
- Pars nervosa

Neurohypophysis (neural structure)

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23
Q

What is the hypothalamic control of the anterior pituitary?

A

Hypothalamic neurons do not extend into the anterior pituitary

Secretion by the anterior pituitary is regulated by hormones produced by neurons in the hypothalamus and secreted in the median eminence

The hypothalamic hormones travel through the hypothalamic-hypophysial portal vessels to reach the glandular cells in the anterior pituitary

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24
Q

What are the cell types in the anterior pituitary and what do they do?

A

5 main cell types:
- Gonadotrophs
- Corticotrophs
- Thyrotrophs
- Somatotrophs
- Lactotrophs

Specialised endocrine cell types

Cell population plasticity to meet changing needs

The differentiation is controlled by signalling molecules and transcription factors

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25
What are the anterior pituitary hormones and their structure, receptor type, signalling pathways and method of action?
a. GH, peptide hormone, cytokine receptor, JAK/STAT, protein synthesis and growth, lipolysis and increased blood glucose b. Prolactin, peptide hormone, cytokine receptor, JAK/STAT, promotes milk production in mammary glands c. ACTH, peptide hormone, GPCR, activation of adenylyl cyclase/cAMP, regulates glucocorticoid production d. MSH, peptide hormone, GPCR, activation of adenylyl cyclase/cAMP, stimulates melanocytes to promote skin pigmentation e. TSH, peptide hormone, GPCR, activation of adenylyl cyclase/cAMP, acts on thyroid gland to promote T4 and T3 secretion f. FSH, glycoprotein, GPCR, activation of adenylyl cyclase/cAMP, promotes gamete production, stimulates oestrogen production in females g. LH, glycoprotein, GPCR, activation of adenylyl cyclase/cAMP, Stimulates sex hormone secretion; ovulation and corpus luteum formation in females, testosterone secretion in males
26
What are endocrine feedback mechanisms in the hypothalamus and anterior pituitary?
Hypothalamus is influenced by signals from the CNS and by feedback signals (most commonly negative) from the anterior pituitary and downstream target glands The anterior pituitary receives feedback signals from the target glands In negative feedback the target gland hormones act to: - Inhibit the production or secretion of releasing hormones by the hypothalamus - Inhibit the response of the anterior pituitary to the hypothalamic releasing hormones
27
What reproductive hormone is in the hypothalamus?
Gonadotrophin-releasing hormone (GnRH)
28
What reproductive hormones are in the anterior pituitary gland?
Luteinising hormone (LH) Follicle-stimulating hormone (FSH)
29
What reproductive hormone is in the posterior pituitary gland?
Oxytocin
30
What reproductive hormones are in the gonads?
Oestrogens and progesterone Testosterone Inhibin Activin Prostaglandin
31
What are the steps of hormonal control of reproduction?
1. Hypothalamus - Gonadotrophin releasing hormone 2. Anterior pituitary - Gonadotrophins; LH and FSH 3. Gonads - Steroids - oestrogen and progesterone - Testosterone
32
What is gonadotrophin releasing hormone (GnRH)?
Peptide hormone consisting of 10 amino acids Synthesised in hypothalamus Derived from post translation modification of precursor molecule
33
What do we know about the action of Gonadotrophin releasing hormone (GnRH)?
Secreted in a pulsatile manner Half-life a few minutes Binds to GnRH receptor (GPCR) on gonadotroph cells in anterior pituitary
34
What do we know about Luteinising Hormone (LH)?
Is a glycoprotein composed of alpha and beta subunits Molecular weight of around 30kDa Half life of around 30mins
35
What is the secretion of LH regulated by?
GnRH Gonadal Steroids
36
What do we know about the secretion of LH?
Pulsatile Pulse frequency is different during the different stages of the menstrual cycle Can have both frequency and amplitude modulation
37
What do we know about follicle-stimulating hormone (FSH)?
Is a glycoprotein composed of alpha and beta subunits Molecular weight of around 30kDa Half life of 3-4 hours
38
What is the release of FSH controlled by?
GnRH Steroids Inhibin/activin
39
What is FSH used for?
The stimulation of follicular development to induce multiple ovulations for embryo transfer
40
Describe the basic process of steroid hormone synthesis?
Cholesterol (C27) ↓ -6c ↓ Progestins (C21) ↓ -2c ↓ Androgens (C19) (CYP19 - Aromatase) ↓ -1c ↓ Oestrogens (C18)
41
What hormones are synthesised in the testes?
Steroid Hormones: - Androgens, mainly testosterone Peptide Hormones: - Inhibin - Activin
42
What is the principle site of androgen production in the testis?
Leydig cells within the testes
43
What do we know about the process of testosterone synthesis?
LH binds on the LHR on Leydig cells, stimulating testosterone production
44
What is the function of testosterone in the testes? The role of FSH?
Testosterone diffuses into adjacent Sertoli cells and binds the androgen receptor (AR) to regulate spermatogenesis FSH binds the FSHR on Sertoli cells, stimulating the production of androgen binding protein (ABP), which helps concentrate testosterone in the testis.
45
What do we know about Androgens?
5-alpha-dihydrotestosterone, testosterone, androstenedione, dehydroepiandrosterone Induce and maintain differentiation of male somatic tissues Induce secondary sex characters of males (deep voice, body hair, penile growth) and body hair of females Promote protein anabolism and somatic growth Support spermatogenesis Influence sexual and aggressive behaviour Regulate secretion of gonadotrophins
46
What are the 2 purposes of the ovary?
Ovary serves a dual purpose: 1. Oogenesis and the production of gametes 2. Synthesis of hormones - Steroid hormones: oestradiol, progesterone - Peptide hormones: inhibit
47
Where do the 2 functions of the ovary occur PRIOR to ovulation?
Oogenesis and hormone production occur in a single struture, the follicle, prior to ovulation.
48
What do we know about the 8 roles of Oestrogens?
Oestradiol, oestriol, oestrone 1. Stimulate growth and activity of mammary gland and endometrium 2. Prepare uterus for sperm transport 3. Prepare endometrium for progestogen action (i.e. induce progesterone receptors) 4. Increase vascular permeability and tissue oedema 5. Regulate secretion of gonadotrophins 6. Associated with sexual behaviour in some species 7. Stimulate secondary sex characteristics of female 8. Required for normal physiologic processes in the heart, muscle, bone, brain and liver
49
What are the main progestogens? What do we know about the 6 roles of progestogens?
Progesterone, 17 alpha-hydroxyprogesterone, 20 alpha-hydroxyprogesterone 1. Regulate gonadotrophin secretion (-ve feedback) 2. Prepare uterus to receive conceptus 3. Depress uterine activity during pregnancy 4. Stimulate growth of mammary glands, but suppress secretion of milk 5. Promote the formation of non-penetrable cervical mucous 6. Neuroprotective effects on CNS
50
What do we know about inhibin and activin?
Belong to the transforming growth factor-beta superfamily Heterodimeric protein hormones Activin produced in gonads, pituitary gland, placenta and other organs Inhibins are secreted by granulosa cells of the ovary in females and Sertoli cells of the testis in males Activin promotes FSH synthesis by gonadotroph cells In the ovarian follicle, activin increase FSH binding and FSH-induced aromatisation Activin participates in androgen synthesis enhancing LH action in the ovary and testis In the male, activin enhances spermatogenesis
51
What is the mechanism of action of inhibin and activin?
Activin binds to serine/threonine kinase receptors which phosphorylate SMAD3 leading to Fshb transcription Activin action is antagonised by: - Follistatin that binds to activin and neutralises it - inhibins that outcompete activins for binding to their receptors.
52
What happens in the follicular phase (regarding hypothalamus-pituitary-ovarian axis)?
Pituitary hormone effect LH and FSH stimulate several follicles to grow GnRH from hypothalamus to anterior pituitary ↓ Increase in FSH and LH from anterior pituitary to follicles of the ovary ↓ = decrease in oestrogen in the endometrium, anterior pituitary and hypothalamus
53
What happens in ovulation (regarding hypothalamus-pituitary-ovarian axis)?
Pituitary hormone effect: LH and FSH stimulate maturation of one of the growing follicles GnRH from hypothalamus to anterior pituitary ↓ EXTREME Increase in FSH and LH in the follicle of the ovary ↓ EXTREME Increase in oestrogen in the hypothalamus and endometrium
54
What happens in the luteal phase (regarding hypothalamus-pituitary-ovarian axis)?
Pituitary hormone effect: LH stimulates formation of a corpus luteum from follicular tissue left behind after ovulation GnRH from hypothalamus to anterior pituitary ↓ Increase in FSH and LH from anterior pituitary to the ovary forming corpus luteum ↓ Decrease in Oestrogen and progesterone from ovarie to hypothalamus, anterior pituitary and endometrium
55
What do we know about oestradiol feedback regulation?
GnRH neurons do not express ERα ERα is expressed in upstream Kisspeptin neurons in the anteroventral periventricular (AVPV) and arcuate (Arc) regions GnRH neurons express the Kisspeptin receptor and respond to Kisspeptin Knockout of ERα in AVPV kisspeptin neurons blunted LH surge but did not alter reproductive cyclicity --> Mediates positive feedback to oestradiol Knockdown of ERα in arcuate kisspeptin neurons disrupted reproductive cyclicity --> mediates negative feedback to oestradiol
56
What are the endocrine changes in pregnancy?
hCG (Mimics LH) ↓ Maintains oestradiol and progesterone from corpus luteum (Maintains early pregnancy) ↓ Suppresses pituitary gonadotrophins ↓ Postpones next cycle of follicle maturation ↓ Maintains early pregnancy ↓ Back to maintains early pregnancy
57
What do we know about Human chorionic somatomammotropin/human placental lactogen (HPL)?
Produced by syncytiotrophoblasts Level rises with pregnancy and is proportional to placental size Mobilises maternal nutrients for foetal needs Breasts: Development of acinar glands for milk production
58
When does steroidogenesis in the foeto-placental unit occur?
Towards the end of the first trimester
59
What does progesterone do and where is it produced towards the end of the first trimester?
Placental production of progesterone takes over from corpus luteum which regresses - Maintains pregnancy - Inhibits smooth muscle cell contraction to prevent premature labour
60
What does Oestrogen do and where is it produced towards the end of the first trimester?
Oestrogen (oestriol) synthesis occurs in the placenta - Increases uterine blood flow - Prepares mother for birth and lactation - Stimulates release of prolactin - Stimulates oxytocin receptor expression in late pregnancy
61
Where does the biosynthesis of cortisol occur towards the end of the first trimester?
In the foetal adrenal gland

Advanced concepts in reproduction (9 decks)

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