The Hypothalamic-Pituitary-Gonadal Axis

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The Hypothalamic-pituitary-gonadal axis (also HPTA) is a way of describing the orchestrated effects of three particular glands in the endocrine system; the hypothalamus, the pituitary, and the gonads. The HPTA is considered critical in the development and regulation of many systems in order for the body to function normally and in particular in the growth, reproductive and immune systems.

In the brain, the hypothalamus is where it all begins. You could consider it the air traffic controller. The hypothalamus secretes a hormone called gonadotropin-releasing hormone (GnRH) and this hormone is delivered to the pituitary gland by means of a blood portal to the front part of the pituitary gland and then acts on the gonadotropes to release two different hormones, the luteinizing hormone (LH) and the follicle stimulating hormone (FSH) which in normal circumstances occurs approximately every 60 to 90 minutes.

The LH and FSH travel through the blood stream and both act on the gonads to produce varying effects including the release of sex hormones and keeping the gonadal integrity.
Like every natural or manufactured hormones, LH and FSH will clear the system at different rates, LH has a shorter half life than does FSH. Blood levels of testosterone have a robust diural (greatest secretion is at night), the circadian pattern of LH is highly individualized and is blunted based on the level of testosterone.

The regulation of the HPTA is done by what is called a negative feedback mechanism. Feedback regulation of LH and FSH secretion at the pituitary level is done by testosterone, dihydrotestosterone (DHT), and estrogens which inhibit the synthesis (manufacturing) and/or release of both gonadotropins (LH and FSH). Both LH and FSH circulate through the blood unbound (meaning they are able to attach to surface receptors) and attach themselves to Leydig and Sertoli cells of the testes respectively. LH regulates the production of steroid hormones via the Leydig cells that reside in the interstitium (between the lining).

As you know, testosterone is the principle male hormone secreted by the testes, with about 7 mg produced per day in adult males. The rate limiting factor in this process is the LH-inducible StAR (steroid acute regulatory) protein and the conversion of cholesterol.

When testosterone is produced it is consider bound or unbound. If it is bound it is bound to two plasma proteins. One is the sex hormone-binding globulin (SHBG) and the second is albumin. In the average young adult male, about 54% of testosterone is bound to albumin, 44% is bound to SHBG, and 2-3% is considered free or unbound. So when you are tested for testosterone, bioavailable testosterone refers to the sum of albumin-bound and free testosterone and is measured by separating SHBG-bound testosterone for the total in the serum.

It should be noted however, serum SHBG levels are increased when there is an increase in estrogen, hyperthyroidism, aging, anorexia nervosa, and prolonged stress (ie. High levels of cortisol). SHBG levels are lowered with androgen treatment, obesity, and hypothyroidism. In conditions with abnormal SHBG levels, the total testosterone level may be misleading. Remember, testosterone levels are diurnal with the highest level being in the morning; this diurnal rhythm is lost when we age.