Hypothalamic–pituitary–gonadal axis in which the hypothalamus and pituitary direct neuroendocrine function. The hypothalamus is located in the brain and secretes GnRH. GnRH travels down the anterior portion of the pituitary via the hypophyseal portal system and binds to receptors on the secretory cells of the adenohypophysis. In response to GnRH stimulation these cells produce LH and FSH, which travel into the blood stream. These two hormones play an important role in communicating to the gonads. In females FSH and LH act primarily to activate the ovaries to produce estrogen and inhibin and to regulate the menstrual cycle and ovarian cycle. Estrogen forms
Pituitary adenoma interacting protein" ("AIP") gene , and duplications in chromosome Xq26.3 that include the "GPR101" gene that also causes X-linked acrogigantism (X-LAG) syndrome. About 15-20% of FIPA families carry a germline "AIP" gene mutation or deletion, and the disease occurs as autosomal dominant with incomplete penetrance, meaning that about 20% of AIP mutation carriers will develop a pituitary adenoma. "AIP" mutation associated pituitary adenomas (either presenting as FIPA or as individual, non familial cases) are usually growth hormone secreting (acromegaly) or prolactin secreting (prolactinoma) adenomas that are large (macroadenomas) and often occur in children, adolescents and young adults. Daly and colleagues