Although the gonads produce hormones that are important for sex development, a network of other glands (the HPG axis) communicates with the gonads to control the levels of these hormones. Many DSDs reflect disturbance of the HPG axis rather than irregularities of gonad development.
As the above discussion indicates, many aspects of sex development—internal ducts, genitals, breasts, body hair, body shape, voice and so on—depend on hormonal signals from the gonads. Early in fetal life, sex steroids are produced automatically by the gonads, but later, gonadal steroid production needs to be triggered by a complex chain of instructions starting in the brain. This chain of instructions involves three glands in the body: the hypothalamus, the pituitary, and the gonads. For this reason, this group of glands and the communication between them is known as the HPG axis.
First, the hypothalamus, a pea-sized gland buried deep within the brain between the temples, produces a hormone known as GnRH. An adjacent, similarly sized gland called the pituitary gland responds to the GnRH signal by producing two more hormones called FSH and LH. It is these hormones that then trigger the gonads to increase steroid hormone production. Importantly, both the hypothalamus and the pituitary are able to respond to circulating levels of androgens and oestrogens, and adjust the production of GnRH, FSH and LH accordingly.
Therefore, any medical condition that arises as a result of atypical androgen or oestrogen levels may not necessarily reflect a problem in gonadal formation, but may instead indicate a blockage elsewhere in the HPG axis. This can relate to hypothalamus structure or GnRH production, to the ability of the pituitary to receive the GnRH signal, to the production of active FSH or LH, or to receiving the FSH or LH signal.
Combined with the fact that a large number of biochemical steps are involved in making steroids in the body, the complexity of the HPG axis provides many points at which typical sexual development can falter and result in DSD.
Last updated: 17 July 2015
Edit history: Author P. Koopman 3/13; revised PK 7/13, 10/13