Our previous studies have proved the presence of substantial amounts of peptidergic nerve fibers in the anterior pituitary of human, monkey, dog, and rat, and synaptic contacts have been demonstrated on corticotrophs and somatotrophs in the dog. The present study is aimed at investigating the synaptic relationship between axons and gland cells in the rat. The substance P-like-immunoreactive nerve fibers were studied immuno-electron-microscopically. They were nonmyelinated and varicose. Typical synaptic contacts between the fibers and every type of the hormone-secreting gland cell could be identified, most frequently on lactotrophs. No synaptic contacts were found on the folliculo-stellate cell. The synaptic contacts were of asymmetrical type with clusters of small round clear vesicles at the presynaptic site and scattered large dense-cored vesicles. This pattern of synaptic relationships was markedly different from that in the dog. The presence of synapses in the anterior pituitary of the rat implies a direct neural regulation of certain cells and strongly supports our hypothesis of neural-humoral dual regulation of this gland.

Our previous studies have demonstrated the presence of substantial amounts of peptidergic nerve ®bres in the anterior pituitary of monkeys, dogs and rats. The nerve ®bres increase in number following adrenalectomy and ovariectomy. Furthermore, typical synapses between nerve ®bres and anterior pituitary glandular cells have been demonstrated in the dog and rat, strongly suggesting the existence of some direct neural regulation. However, it is dif®cult to evaluate the functional importance of synapses or nerve terminals in general, unless quantitative data can be provided. The present study therefore aimed to quantify the number of terminals or varicosities in the anterior pituitary of the rat and its changes following adrenalectomy. Nerve terminals or varicosities were identi®ed by their synaptophysin (SYN)-like immunoreactivity. Under the light microscope, SYN-like immunoreactivity appeared mainly as dots, mostly among glandular cells, and some were found distributed along blood vessels. SYN-like immunoreactive dots were found under the electron microscope to be localized in the nerve terminals or varicosities. Synapse-like contracts between the nerve terminals or varicosities and the glandular cells could be identi®ed. The number of SYN-like immunoreactive nerve terminals or varicosities was then counted under the light microscope. There were as many as 12424.2t2941.5 and 20700.4t6128 (meantSD) nerve terminals or varicosities per anterior pituitary of normal and adrenalectomized rats, respectively. The increase in number following adrenalectomy was statistically signi®cant. It is concluded that nerve ®bres may play an important role in the regulation of the anterior pituitary.