L1. Regulation of the Reproductive Cycle

Regulation of Reproduction, Innervations, Hormones & Target Tissues

Hormones

Hormones originate from endocrine glands or nerves

Hormones enter the blood and act on cells with specific receptors in target tissues to produce new products or other hormones

Protein hormones act via plasma membrane receptors and exert effects in the cytoplasm of the cell

Steroid hormones act through nuclear receptors to cause transcription and translation resulting in the production of new proteins

Protein and steroid hormones cause changes in the function of the target cells

The strength of hormone action depends on:

  • pattern and duration of secretion

  • half-life

    • determines how long it will act

  • receptor density

    • affects the degree to which hormones can promote up-regulation or down-regulation of synthesis

  • receptor-hormone affinity

    • agonist: have similar molecular structure that bind to specific receptor and cause same (or better) biological effect as native hormone
    • antagonist: have greater affinity to receptor but promote weaker activity than native hormone

Metabolism of hormones

Steroids: metabolised by liver and excreted in urine and faeces

Protein hormones: degraded in liver and kidneys

Detection of Hormones

can be detected in physiological fluids: blood, saliva, urine, lymph, tears, faeces, milk using radioimmunoassay (RIA) and ELISA technology

Reproduction

Reproduction is regulated by the interplay between the nervous system and the endocrine system

The nervous and endocrine systems interact in a consistent display of teamwork to initiate, coordinate and regulate all reproductive function

The fundamental responsibility of the nervous system is to translate or transduce external stimuli into neural signals that bring about change in the reproductive organs and tissues

Neural control is exerted by:

  • simple neural reflex
    • employs nerves that release their neurotransmitters directly onto the target tissue, which is directly innervated by neurons
  • neuroendocrine reflex
    • requires neurohormone (substance released by neuron) to enter the blood and act on remote target tissue
    • neurons releasing neurotransmitters may be called neurosecretory cells

The difference between the simple neural reflex and neuroendocrine reflex is the type of delivery system

Neural reflexes and neuroendocrine reflexes cause rapid changes in the target tissue

Another type of neuron is widespread throughout the central nervous system: inhibitory neuron (inhibits other neurons)

  • Excitatory neurons
    • use excitatory neurotransmitters
    • increase the probability of postsynaptic action potential
  • Inhibitory neurons
    • use inhibitory neurotransmitters
    • decrease the probability of postsynaptic action potential
    • block or stop the action of the other excitatory neurons

The probability that the postsynaptic neuron will fire is controlled by the ratio of presynaptic excitation: presynaptic inhibition

Hypothalamus

The hypothalamus is the neural control centre for reproductive hormones

It is a complex portion of the brain consisting of clusters of nerve cell bodies called hypothalamic nuclei

Groups of hypothalamic nuclei that influence reproduction are called the surge centre and the tonic centre

Neurons in the hypothalamus communicate with the anterior lobe of the pituitary utilising a special circulatory modification known as the hypothalamohypophyseal portal system

Axons from the cell bodies of the surge and tonic centres extend into the pituitary stalk region where the nerve endings (terminal buttons) terminate on the sophisticated and highly specialised capillary network (hypothalamohypophyseal portal system)

The posterior lobe of the pituitary gland does not have a portal system; Neurohormones are deposited directly into capillaries in the posterior lobe of the pituitary

Endocrine Control vs. Neural Control

Endocrine control is generally slower but lasts longer than neural control

The endocrine system relies on hormones to cause responses

Hormone: a substance produced by a gland that acts on a remote target tissue to bring about a change in the target tissue

  • alteration in metabolism
  • synthetic activity
  • secretory activity

Hormonal control has durations of minutes, hours, or even days

Extremely small quantities of a hormone can cause dramatic physiological responses

hormones act at blood levels ranging from nanograms (10^-9) to picograms (10^-12) per millilitre of blood

The ability to measure extremely small quantities of hormones has brought about an explosion of knowledge regarding the quantities, patterns of secretions and the roles of hormones as they relate to reproductive processes

Hormones have relatively short half-lives

Short half-lives are important because once the hormone is secreted and released into the blood and causes a response, it is degraded so that further or unnecessary responses do not occur

When hormones are continually produced (such as progesterone during pregnancy), the action brought about by the hormone continues for as long as the hormone is present

Positive and Negative Feedback

Negative feedback

  • primary control mechanism
  • e.g. suppression of GnRH neurons when progesterone is high
    • increased P4 → decreased GnRH → decreased FSH/LH → little follicular development
    • when progesterone is high GnRH neurons secrete only basal levels of GnRH

Positive feedback

  • e.g. stimulation of GnRH neurons when oestrogen is high
    • E2 higher than threshold → greatly increased GnRH → greatly increased LH → stimulation of ovulation

Tonic centre

  • responds mainly to negative feedback

Surge centre

  • responds mostly to positive feedback of oestradiol

NB: progesterone in females exerts strong negative feedback on both surge and tonic centres, but mostly exerts its effect on the tonic centre

Reproductive Hormones

  • act in minute quantities
  • have short half-lives
  • bind to specific receptors
  • regulate intracellular biochemical reactions

Hormones are classified by their:

  • source
    • Reproductive hormones originate from:
    • hypothalamus
    • pituitary
    • gonads
    • uterus
    • placenta
  • mode of action
    • neurohormones
    • synthesised by neurons
    • released directly into the blood
    • cause a response in target tissues elsewhere in the body
    • target tissue has cellular receptors for neurohormone
    • e.g. oxytocin
    • releasing hormones (can also be classified as neurohormones)
    • synthesised by neurons in the hypothalamus
    • cause the release of other hormones from the anterior pituitary
    • e.g. GnRH
    • Gonadotropins
    • released by gonadotroph cells at the anterior pituitary
    • stimulate gonads
    • e.g. FSH, LH
      • hCG and eCG are produced by the early embryo (conceptus) which cause the stimulation of the maternal ovary
    • Pregnancy maintenance hormones
    • high concentrations during pregnancy
    • e.g. placental lactogen promotes the development of the mammary gland and is lactogenic
    • General metabolic hormones
    • promote metabolic wellbeing
    • e.g thyroxin from thyroid gland → regulates metabolic rate
    • e.g. adrenal corticoids from the adrenal cortex → mineral metabolism to the regulation of inflammatory responses
    • e.g. growth hormone (somatotropin) from the anterior lobe of the pituitary → regulates growth, lactation, protein metabolism
    • Luteolytic hormones
    • causes the corpus luteum to stop functioning
  • biochemical classification
    • peptides
    • small molecules with few amino acids joined by peptide bonds
    • most important: GnRH
    • glycoproteins
    • polypeptide hormones containing carbohydrate moieties (molecular weight from several hundred to 70,000)
    • some are composed of two side-by-side polypeptide chains that have carbohydrates attached to each chain
      • polypeptides are designated as α and β subunits
    • e.g. inhibin
      • contains α and one of two β subunits (βA,βB)
      • activity regardless of which β subunit is present
      • suppresses FSH secretion
    • e.g. activin
      • consists of two β subunits
      • causes opposite of inhibin in vitro
      • release of FSH in pituitary cells in culture
    • e.g. prolactin
      • consist of a single polypeptide chain not from α and β subunits
    • steroids
    • all have a common cyclopentanoperhydrophenanthrene nucleus
    • synthesised from cholesterol
    • prostaglandins
    • lipids consisting of 20-carbon unsaturated hydroxy fatty acids that are derived from arachidonic acid
    • stimulate uterine smooth muscle
    • influence lipid metabolism
    • mediate inflammation
    • e.g. PGE2 lowers blood pressure
    • e.g. PGF2 increases blood pressure

Pheromones

Pheromones are another class of substances that cause remote effects

They secreted to the outside of the body

Generally, they are volatile and detected by the olfactory system by members of some species

They cause specific behavioural or physiological responses by the percipient

Pheromones are known for:

  • onset of puberty
  • identification of females in oestrus by males
  • other behavioural traits