Determinants of Hormone Control

In my last post for PHYL3004, I spoke about one class of hormones (the steroids). In this post, I will be covering eicosanoid and protein hormones.

Eicosanoids

Eicosanoid hormones are derived from arachidonic acid, which is a constituent of cell plasma membranes. Eicosanoids include leukotrienes, thromboxanes, prostacyclin and prostaglandins. I have covered all of these hormones here. The most important eicosanoids for the reproductive system are prostaglandins, which are involved in ovulation and uterine contractions.

Proteins

Proteins are chains of amino acids. I've written far more detail than you need to know for this unit about protein structure here, and about protein synthesis here. Proteins are hydrophilic and generally don't need binding proteins to transport them around the blood. They cannot, however, readily diffuse into cells, so they usually bind to an external membrane-bound receptor, which then activates some second messengers. These second messengers usually increase calcium levels or act as transcription factors in order to carry out their effects.

Gonadotrophins

The main gonadotrophins that you need to know are luteinising hormone (LH), released from the anterior pituitary, follicle-stimulating hormone (FSH), also from the anterior pituitary, and human chorionic gonadotrophin (hCG), from the syncytiotrophoblast (a structure formed during implantation of the blastocyst into the endometrium). All of these hormones have two chains (an alpha- and a beta-chain), and the alpha-chain is the same for all of the hormones. I've written more about LH and FSH here. hCG acts on luteal cells in the ovary to maintain progesterone, and on Leydig cells in the fetal testis in order to increase androgen production and testis development.

Somatomammotrophins

Somatomammotrophins are involved in tissue growth and function. The main somatomammotrophin is prolactin, released from the anterior pituitary. It is involved in lactation. If prolactin levels are high, fertility is suppressed.

Cytokines

Cytokines are often thought of as the main signalling molecules for the immune system, but they can do more than that. Inhibin is a cytokine that is involved in the reproductive system. It is released from granulosa cells (in females) or Sertoli cells (in males), and is involved in guiding gamete development and in gonad-pituitary interactions.

Oligopeptides

Oligopeptides are small peptides that are usually derived from cleaving a larger polypeptide precursor. Examples include GnRH, a highly-conserved 10 amino acid peptide that controls gonadotrophin secretion, and oxytocin, a posterior pituitary hormone involved in parturition, milk letdown and bonding.

Determinants of Hormone Action

The main determinants of hormone action are transport, blood concentration, secretion patterns and receptor expression, so let's get started!

Transport

As mentioned before, steroid hormones generally need a carrier protein to move around the blood, whereas proteins can normally move around by themselves. Only unbound hormones are biologically active.

Blood concentration

The blood concentration of hormone = production rate / clearance rate. Clearance may be due to hormone metabolism, which mainly occurs in the liver, but a small amount of metabolism can occur in the lung during respiration.

Secretion patterns

Most reproductive hormones are secreted in a pulsatile (on/off) manner. Some may follow a kind of circadian (~24hr) rhythm. Testosterone has a somewhat circadian pattern in younger males, but not so much in older males. However, the significance of this is still unknown. Pulsatile release is very important for some hormones, such as GnRH. If GnRH was secreted continuously, receptors would be down-regulated, and LH (a hormone "downstream" of GnRH in the signalling pathway) would decrease.

As you hopefully know by now, female fertility is episodic, with a monthly cycle in ovarian activity. Meanwhile, males pretty much have repeated pulsatile release of hormones from puberty onwards.

Receptor expression

Hormones can only have an effect if they bind to their target. Therefore, the number of targets (receptors) present is related to the strength of the effect. As I just mentioned, continuous release of GnRH can result in downregulation of GnRH receptors and therefore a decrease in the effectiveness of this hormone. Progesterone has the opposite effect: it can upregulate progesterone receptors on the endometrium.

Control of the Endocrine System

The main control systems are simple control, negative feedback, positive feedback and inhibitory control.

Simple control

In simple control, one hormone stimulates another. For example, GnRH stimulates LH.

Negative feedback

See previous post: Control Systems 1

Both males and female reproductive systems use negative feedback.

Positive feedback

See previous post: Control Systems 1

The female reproductive system can use positive feedback in ovulation and in childbirth.

Inhibitory control

In inhibitory control, an inhibitory factor prevents the release of a hormone. For example, dopamine acts as an inhibitory factor preventing the release of prolactin. Therefore, dopamine agonists such as bromocriptine may be considered in the treatment of hyperprolactinaemia (see here).