Pituitary structure and function

There are three lobes to the pituitary gland (hypophysis): the anterior lobe, the posterior lobe and the pars intermedia, a small intermediate structure lying between the anterior and posterior lobe that is actually a subdivision of the anterior lobe.

The pituitary is connected to the brain via a small branch of tissue known as the pituitary stalk or infundibulum. The posterior pituitary serves mainly as a storage site for two hormones produced in the hypothalamus: oxytocin and arginine vasopressin (also known as antidiuretic hormone, ADH). In contrast, the anterior pituitary produces tropic hormones under the regulatory control of the hypothalamus. This control is mediated by neuroendocrine signals from the hypothalamus that travel through rich vascular connections surrounding the pituitary stalk. Blood flowing through this highly vascular plexus delivers signals to the anterior pituitary gland, regulating production and release of its protein products.

There are five cell types in the anterior pituitary that are associated with tropic hormone production: gonadotropes, lactotropes, somatotropes, thyrotropes and corticotropes. These specific cells are responsible for production and secretion of: follicle-stimulating hormone (FSH) and luteinizing hormone (LH); prolactin; growth hormone; thyroid-stimulating hormone (TSH); and adrenocorticotropic hormone (ACTH), respectively. The thyrotropes and gonadotropes closely resemble each other histologically because their secretory products, LH, FSH and TSH, are all glycoprotein hormones that stain with carbohydrate-sensitive reagents. LH and FSH are produced by a single cell type, allowing coupled secretion and regulation by a single releasing factor.

Control of pituitary gland activity comes largely from the hypothalamus with important direct modulation by feedback mechanisms. The hypothalamic nuclei associated with reproduction include the supraoptic, paraventricular, arcuate, ventromedial and suprachiasmatic nuclei. Neurons in two less well-defined areas, the medial anterior hypothalamus and the medial preoptic areas, are also involved. The magnocellular (large) neurons that originate in the supraoptic and paraventricular nuclei project into the posterior pituitary and produce the hormones vasopressin and oxytocin. The parvocellular (small) neurons found in the paraventricular, arcuate and ventromedial nuclei and the periventricular and medial preoptic areas produce regulatory peptides that control the tropic hormones produced by the anterior pituitary.

Those cells in the hypothalamic nuclei that regulate the pituitary have several functions. They receive signals from higher centers in the brain, generate neural signals of their own and have neuroendocrine capabilities. The higher areas of the brain that connect to the hypothalamic nuclei involved with reproduction are the locus ceruleus, the medulla and pons, the midbrain raphe, the olfactory bulb, the limbic system (amygdala and hippocampus), the piriform cortex and the retina. Endogenous opioids also influence hypothalamic function.

The neuroendocrine signals generated within the hypothalamus are mediated by peptide-releasing factors that travel through the hypothalamic–pituitary portal system to their site of action in the pituitary gland. Gonadotropin-releasing hormone (GnRH) is the key tropic hormone for regulating gonadotrope cell function and hence, reproduction. A key neural signal in human reproduction arises from what is known as the GnRH pulse generator. The mechanism by which pulsatile GnRH release controls gonadotropin synthesis and secretion remains poorly defined. At baseline, GnRH secretes from the hypothalamus in pulses at a frequency of approximately one pulse per hour. GnRH pulse frequency is most rapid in the follicular phase, slightly slower in the early luteal phase and slowest in the late luteal phase of the female menstrual cycle. In general, rapid pulse frequencies favor LH secretion and slower pulse frequencies favor FSH release. The relationship between pulse frequency and LH and FSH secretion appears to exist in both women and men. Continuous GnRH release inhibits gonadotrope function. This is the basis for the downregulating activities of long-acting exogenous GnRH agonists and antagonists.

Thyrotropin-releasing hormone (TRH) and prolactin inhibitory factor (PIF) also have roles in reproductive regulation. Those hypothalamic neuroendocrine peptides that control growth hormone (GH) and ACTH secretion are less directly related to reproduction.