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In vitro short-term effects of SMS 201-995, bromocriptine and TRH on growth hormone cell morphology from human
J García García1, L Jiménez Reina, P P García Luna
1Dpto. Ciencias Morfológicas, Universidad de Córdoba, Spain.
Abstract:
This study reports, by immunocytochemistry, ultrastructure and morphometry, the in vitro effects of SMS 201-995 (10 nM), bromocriptine (1 microM) and TRH (10 microM) on the morphology of cells from two acromegalic patient adenomas containing immunoreactive growth hormone (GH). By electron microscopy, one tumor presented numerous large secretory granules (densely granulated growth hormone cell adenoma) while they were scarce and small in the other (sparsely granulated growth hormone cell adenoma); fibrous bodies could be seen in the specimen and in vitro. In the sparsely granulated growth hormone cell adenoma, TRH produced an increase in endoplasmic reticulum surface density compared to the other cultures. Bromocriptine increased the number and decreased the secretory granule diameters, while SMS 201-995 produced no significant changes in the same time. In the densely granulated growth hormone cell adenoma, the three substances increased the number of granules. TRH increased the mitochondrial volume density and endoplasmic reticulum surface density (with respect to the other cultures). SMS 201-995 decreased the mitochondrial and lysosome volume densities and endoplasmic reticulum surface density. We conclude that 1) TRH produces in cultured cells of both adenoma types an increase in cellular activity. 2) In cultured sparsely granulated growth hormone adenoma cells, bromocriptine has a stronger inhibitory effect than SMS 201-995. In cultured densely granulated growth hormone cells adenoma, bromocriptine has smaller inhibitory effect than SMS 201-995.
Insights
This study investigated the in vitro effects of SMS 201-995, bromocriptine, and TRH on growth hormone (GH) adenoma cells. Results show varying impacts on cellular activity and secretory granules, offering insights into acromegaly treatment.
Area of Science:
- Endocrinology
- Cell Biology
- Oncology
Background:
- Acromegaly is a disorder caused by excess growth hormone (GH).
- GH-secreting pituitary adenomas are the primary cause of acromegaly.
- Understanding cellular responses to treatment is crucial for managing acromegaly.
Purpose of the Study:
- To investigate the in vitro effects of SMS 201-995, bromocriptine, and thyrotropin-releasing hormone (TRH) on growth hormone (GH) secreting pituitary adenoma cells.
- To compare the efficacy of these agents on different types of GH adenomas (densely vs. sparsely granulated).
Main Methods:
- Immunocytochemistry, ultrastructure, and morphometry were used to analyze cell morphology.
- Primary cell cultures from two acromegalic patient adenomas were treated with SMS 201-995, bromocriptine, and TRH.
- Electron microscopy assessed changes in secretory granules, endoplasmic reticulum, and mitochondria.
Main Results:
- TRH increased cellular activity in both adenoma types.
- Bromocriptine showed a stronger inhibitory effect on sparsely granulated adenoma cells compared to SMS 201-995.
- SMS 201-995 had a greater inhibitory effect on densely granulated adenoma cells than bromocriptine.
Conclusions:
- TRH generally increases cellular activity in GH adenoma cells.
- Bromocriptine and SMS 201-995 exhibit differential inhibitory effects based on adenoma granulation patterns.
- These findings provide insights into the differential cellular mechanisms of acromegaly treatments.