Structure-function correlates in the corticotropes of the anterior pituitary.

Investigators have described changes in pituitary corticotropes that correlate with changes in the physiological state of the animal. The stellate subtype degranulated and enlarged initially after adrenalectomy. This was followed by repopulation of the granules during the first 3 weeks after surgery with larger granules. There was also an increase in the percentage of corticotropes. More recent studies have shown that chronic stimulation with corticotropin-releasing hormone (CRH) produces some of the same changes; however, the magnitude differs because of corticosterone feedback. Corticotropes are heterogeneous in size, shape, storage patterns, and secretory responses. Specific changes are evident within a short time after stimulation as well. Their average cellular area increases within 1-2 h of stimulation by CRH in vitro or cold stress in vivo. Whereas many corticotropes acutely stimulated by cold or a novel environment are better granulated, others are depleted of granules. Cold stress for 30 min also stimulates an increase in the percentage of immunoreactive corticotropes and cells that bind CRH or arginine vasopressin (AVP). Secretagogues like CRH or epidermal growth factor (EGF) act in vitro to increase percentages of cells that store adrenocorticotropin (ACTH) or express mRNA for pro-opiomelanocortin. AVP or angiotensin II (A-II), or their activated second messengers, also increase percentages of cells that bind CRH and store ACTH. Inhibition of ACTH secretion by ion channel blockers or corticosterone has potent inhibitory effects on percentages of CRH-bound cells. AVP binding is not affected. Some of the inhibitory states reduce the average area of corticotropes. However, about 30% of the cells remain unaffected by these inhibitors. The rapid changes in cell percentages with the different treatments have led workers to postulate the existence of reserve cells that may be sensitive to certain levels of types of stimuli. Several candidate reserve cells are proposed. One group of cells that store ACTH with gonadotropins may function in the proestrous female to stimulate adrenal progesterone. Another multihormonal cell may function during cold stress to release both ACTH and thyroid-stimulating hormone (TSH) under the influence of AVP. There may be subpopulations of corticotropes that act in synchrony with other cell populations. They may be awaiting the proper type or combination of secretagogues to support the pituitary-adrenal and other axes.