Alteration of the mammotroph Golgi complex by the dopamine agonist 2 BR‐α‐ergocryptine (CB‐154) in ovariectomized estrogen primed rats

Abstract

The present study examined the acute effects of 2 Br-alpha-ergocryptine (CB-154, a dopamine agonist) on mammotroph organelles during prolactin (PRL) suppression. Ovariectomized estrogen-primed rats received a single injection (sc) of 0.5 mg CB-154 and the animals were killed at intervals following injection. The anterior pituitary glands were fixed for electron microscopy and immunocytochemistry was used to confirm mammotroph identification. Serum PRL levels were determined by RIA. Following CB-154 administration, serum PRL was significantly (P less than 0.05) reduced within 15 minutes and was suppressed (P less than 0.01) to ovariectomized levels at 2 and 6 hours. A stereological analysis of mammotrophs in the central regions of the anterior pituitary showed that the Golgi complex volume was significantly (P less than 0.05) reduced at 2 hours after CB-154 treatment. However, the Golgi complex volume had recovered by 6 hours post CB-154 injection. In addition, the volumes of the mammotroph cells, the mature secretory granules, and the secondary lysosomes had significantly increased by 6 hours. There were no significant changes in any of the organelles following CB-154 in the mammotrophs from the peripheral regions of the gland. These studies show that the Golgi complex is especially susceptible to acute morphological changes induced by bromocryptine and that the mammotrophs in the central regions are more responsive to CB-154 than those in the peripheral regions.

Gene ontology fuzzy-enrichment analysis to investigate drug mode-of-action

“…The fuzzy intersection of up-regulated genes contained 425 genes while the down-regulated one contained 335 genes. The fuzzy enriched GO:terms (reported in table 4) show the interactions between estrogens and the Golgi apparatus [13,14] and the down-regulation of genes involved in metabolic processes of organic compounds interacting with estrogens (cobalamin, porphyrin and others). So, also in this case the fuzzy enriched GO:terms were strictly linked to the MoA of the analyzed drugs.…”