CHAP 5 Continued!!! (regulation of reproduction)

Kisspepins

• “gatekeeperes” for GnRH

• neuropeptides by hypothalamus

• appears to act directly on GnRH neurons to stimulate GnRH secretion

• Important regulator of sexual differentiation of the brain (puberty)

• Important regulator of seasonality

• Affected by pheromones, stress, photoperiod, nutrition, age, etc.

Reproductive hormones

• act in minute quantities

• have short half-lives

• bind to specific receptors

• regulate intracellular biochemical reactions

half-life

the time taken for the radioactivity of a specified isotope to fall to half its original value.

Reproductive hormones classified by:

Source → ex. pituitary hormones (FSH, LH, oxytocin, prolactin)

Mode of action → Gonadotropins (FSH, LH)

Biochemical classification → Glycoproteins (FSH, LH)

Reproductive hormones must first interact with specific __________

Target Tissue

• receptors

• binding w specific receptor initiates series of intracellular biochemical reactions

Regulation of reproductive hormones

biochemical reactions

• Target cell - only secretes substance in response to hormone

  • doesn’t secrete if hormone is not present

repro hormones originate from:

• hypothalamus

• pituitary

• gonads

• uterus

• placenta

Functions of reproductive hormones

• Release of other hormones - releasing hormones

• stimulation of the gonads - gonadotropins

• sexual promotion - steroids

• pregnancy maintenance

• luteolysis - regression of CL

Repro horm classification: Tissues of Origin

Hypothalamus → GnRH

Pituitary → FSH, LH, prolactin, (oxytocin stored)

Gonadal hormones → estrogens, progesterone, inhibin, testosterone

• Uterine hormone prostaglandin

• lactocrine signaling (relaxin transported via milk)

Repro horm classification: Modes of action - Neurohormones

synthesized by neurons, released directly into blood to target tissues (oxytocin)

Repro horm classification: Modes of action - Releasing hormones

synthesizes by neurons in hypothalamus (GnRH)

Repro horm classification: Modes of action - Gonadotropins

Hormones synthesized and secreted by specialized cells in the antirior lobe of the pituitary gland

“tropin” → to nourish

FSH & LH

Repro horm classification: Modes of action - Sexual promoters

secreted by gonads

• stimulate reproductive tract

• regulate function of the hypothalamus

• regulate reproductive behavior

• development of secondary sex characteristics

**Driving force for ALL reproductive function**

• Estrogen, testosterone, human chronic gonadotropin (hCG), equine chronic gonadotropin (eCG) are secreted by early embryo (conceptus)

• progesterone, placental lactogen

Repro horm classification: Modes of action - General metabolic hormones

promote metabolic well-being

• thyroxin, adrenal corticoids, GH

• Indirect effect on reproduction

Repro horm classification: Modes of action - Luteolytic hormones

destroy CL

• prostaglandin F2⍺

Repro horm classification: Biochemical structure - Peptides

small; only a few amino acids joined by peptide bonds

• GnRH (10 aa)

• Prolactin (198aa; not glycosylated)

Repro horm classification: Biochemical structure - Glycoproteins

Polypeptide hormones - contain carbohydrate moieties

• FSH, LH, inhibin

Carbohydrate Moieties

Sugar structure (monosaccharide, disaccharide, or oligosaccharide) dispersed along each subunit of glycoprotein

• thought to prolong half-life and protect from short-term degradation

• more glycosylation (more CHO units); the longer the half-life

• not effective when given orally - degraded by proteolytic enzymes in digestive tract

Repro horm classification: Biochemical structure - Steroid

common molecular nucleus

• 4 carbon rings

• synthesized from cholesterol

• series of complex pathways - many enzymatic conversions

• sexual promoters → estradiol, progesterone, testosterone

Repro horm classification: Biochemical structure - Prostaglandins

active, rapidly degenerate in blood (half life = seconds)

• PGF2⍺ and PGE2 - control ovulation

Pheromoes

substances that are secreted to the outside of the body

• detected by olfactory system (vomeronasal organ) by members of same species

• Cause specific behavioral or physiological responses

  • onset of puberty, detection of estrus

Target tissues

Only certain cells with specific receptors are capable of responding to a hormone

• even though every cell in the body may be exposed to it

• receptors have affinity for specific hormone and bind to it

Protein hormones - plasma membrane receptors

Once receptor binds the hormone, target tissue performs new function

• often secretes another hormone that acts on a new target tissue

Protein hormones - plasma membrane receptors: STEPS

1. Hormone-receptor binding

2. Adenylate cyclase activation

3. protein kinase activation

4. synthesis of new products

STEP 1

1. Hormone-receptor binding

• surface of target tissues

• sparse

• specific shapes - fit together

STEP 2

2. Adenylate Cyclase Activation

• G-protein

• Membrane bound

• Converts ATP to cyclic AMP

  • Cytoplasm

  • cAMP = “secondary messenger” (primary messenger = hormone)

STEP 3

3. protein kinase activation

• control enzymes

• activate other enzymes in cytoplasm that convert substrates into products

• regulatory and catalytic subunits

STEP 4

4. Synthesis of new products

• generally secreted

• specific functions that enhance reproductive processes

  • FSH and LH bind to follicle cells - synthesis of estradiol

  • steroids simply diffuse through plasma membrane

Steroid hormones

2 types of receptors:

A. Fast response → seconds to minutes

B. Slow response → days to weeks

Fast response steroid

Similar pathway as protein hormones:

1. hormone-receptor binding

2. adenylate cyclase activation

3. protein kinase activation

4. changes in Ca++ channel permeability

• diffuses across plasma membrane into interstitial spaces and blood

Slow response steroid

1. steroid transport

2. movement through the cell membrane and cytoplasm

3. binding of steroid to nuclear receptor

4. mRNA synthesis and protein synthesis

1. steroid transport

Transported in blood by comples system

• not water soluble

• cannot be transported as free molecules

• must attach to molecules that are water soluble

• transport proteins → helps to extend their half-life

2. movement through the cell membrane and cytoplasm

Dissociates with transport protein

• diffuses through plasma membrane

• lipid soluble

• diffuses through cytoplasm and into nucleus

3. binding of steroid to nuclear receptor

similar to protein receptor binding - must “fit” together

steroid0receptor complex = transcription factor

initiates DNA-directed messenger RNA synthesis (transcription)

4. mRNA synthesis and protein synthesis

New mRNA leaves nucleus and attaches to ribosomes

“STRENGTH” of hormone action

1. pattern and duration of secretion

2. half-life

3. receptor density

4. receptor-hormone affinity

Pattern and duration of secretion - Episodic secretion

Associated with hormones under nervous control

• when nerves in hypothalamus fire, neuropeptides are released in a sudden burst/pulse

• “fast”

• pulsatile secretion

Pattern and duration of secretion - Basal secretion

hormone level stays low, but fluctuates with low amplitude pulses

• GnRH secretion from tonic center

• “background”

Pattern and duration of secretion - Sustained secretion

hormone level remains elevated

• relatively steady, stable fasion for long period of time (days, weeks)

• Steroids (think progesterone during pregnancy)

• “consistent”

Half-life

Different life expectancies

rate at which hormone is cleared from the circulation

• seconds: PGF2⍺

• days: eCG

Determined by rate of metabolism within body

• metabolized/inactivated by liver and excreted in urine and feces

Receptor density

Changes between cell type and function

can be influenced by nutrition and body condition

hormones may promote synthesis of receptors for other hormones (or themselves)

• FSH promotes the synthesis of LH receptors

the more receptors = higher potential for response

Receptor affinity

the greater the affinity of the hormones for the receptor, the greater the biological response

Analogs:

• agonists and antagonists

• bind to specific receptor

• interferes with native hormone action

Measuring hormones

Hormones can be detected in blood, saliva, milk, urine, tears, and feces

• RIA - radioimmunoassay

  • radioactive hormones compete with same hormone in blood

  • requires specialized labs, isotope detection equipment and expensive disposal

• ELISA - enzyme-linked immunosorbent assay

  • series of steps to determine presence or absence as well as quantity

  • Minimal training, no health/safety hazards, relatively inexpensive

    • over the counter pregnancy test

    • SARS-CoV-2 antibody test (COVID)