The hypothalamo-pituitary axis and oral contraceptive use in women

Hypothalamo-Pituitary Axis

In order to control an individual's reproductive or gonadal hormones, the hypothalamo-pituitary axis needs to function properly. This axis is made up of the hypothalamus and the pituitary working together in order to regulate the amount of hormone controlled and synthesized. The hypothalamus secretes the hormone gonadotropin-releasing hormone (GnRH) into the hypothalamic-pituitary portal system in pulses, allowing it to stimulate gonadotroph cells of the anterior pituitary. Through G. protein-coupled receptors, the stimulation and signal is amplified, allowing for a larger synthesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (Patton & Thibodeau, 2012). These two hormones have different effects in males and females. In males, LH stimulates the synthesis of testosterone in Leydig cells which then stimulates androgen binding protein (ABP) that is needed for the production of sperm in the testes. In females, LH stimulates thecal cells in order to eventually produce estrogen; this process is heavily influenced by FSH. Although they do work differently in the different sexes, they control the synthesis and secretion of the main gonadal hormones, estrogen and testosterone (Patton & Thibodeau, 2012). Because GnRH is released in pulses, it has better control over how much of the hormone gets released in order to start and continue the process. There is a positive feedback loop once GnRH is stimulated and then released. As a consequence, this increases the release of LH and FSH, but once enough estrogen and testosterone are synthesized, a negative feedback loop is initiated and the release of GnRH is then inhibited; this will therefore inhibit the release of LH and FSH, and the production of estrogen and testosterone (Patton & Thibodeau, 2012). However, once the levels of these essential gonadal hormones are too low, the process repeats itself and the hypothalamo-pituitary axis is once again initiated.

These physiological mechanisms were exploited in order to develop the oral contraceptive pill that worked by controlling the hormone levels in females in order to trick the body into believing that it is already pregnant; this prevents ovulation from occurring, therefore making it nearly impossible for a sperm to be able to fertilize an egg. There are two types of steroidal oral contraceptives: combination estrogen-progestin and progestin-only (Patton & Thibodeau, 2012). Combination estrogen-progestin oral contraceptives suppress the release of GnRH, LH, and FSH, which inhibits the follicular development portion of the menstruation cycle; this means that no ovulation will occur. Because of this co-administration, alterations in tubal peristalsis, endometrial receptivity, and cervical mucus secretions occur, therefore preventing the egg, if it is indeed released, from implanting itself in the endometrial wall of the uterus. The thickness of the wall is determined by the release of LH and FSH during the normal menstrual cycle, however oral contraceptives inhibit this release and instead the estrogen-progestin combination control the endometrial lining directly. Estrogen thickens up the wall, however, too much estrogen alone can cause abnormal cell growth and could potentially lead to cancer; combining it with progestin helps maintain a balance and prevent too much growth of the wall (Patton & Thibodeau, 2012). Progestin-only contraceptives do not prevent ovulation at all times, but instead alter the pulsating release of GnRH, decreasing the anterior pituitary glands responsiveness to GnRH, and preventing as much LH and FSH from being released. An increase in just progestin, without estrogen, causes the cervical mucus and endometrial lining peristalsis to be increased. This results in the inability of the egg to implant itself onto the uterus wall, and preventing fertilization to occur (Patton & Thibodeau, 2012). This entire process, that is, the ability of oral contraceptives to work is solely dependent on the exploitation of the hypothalamo-pituitary axis. By altering the synthesis and secretion of the hormones controlled by this system, oral contraceptives are able to be effective in preventing pregnancy.