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Effects of a depot formulation of the GnRH agonist leuprorelin on the ultrastructure of male rat pituitary gonadotropes
- Source :
- Archives of histology and cytology. 70(2)
- Publication Year :
- 2007
-
Abstract
- To clarify the acute and chronic effects of GnRH agonists on pituitary gonadotropes, changes in the ultrastructure of male rat gonadotropes were examined immunocytochemically and morphometrically after the administration of a one-month depot formulation of the GnRH agonist, leuprorelin. Immediately after the depot administration, the relative amounts of secretory granules drastically decreased in gonadotropes concomitantly with a marked increase in the plasma LH level. After the acute hyperstimulated phase, secretory granules in gonadotropes were gradually restored although the newly synthesized granules were less densely immunolabeled for LHbeta; their relative amounts and sizes were still significantly smaller than the controls after depot treatment for 28 days. Eighty-four days after the leuprorelin depot administration, however, the ultrastructural characteristics of pituitary gonadotropes appeared to recover as observed in controls: there were no significant differences in the relative amounts, sizes, and labeling densities for LHbeta of secretory granules, and the amounts of chromogranin A (CgA) and secretogranin II (SgII) were restored in secretory granules to control levels. When the rats were repeatedly treated with the leuprorelin depot at intervals of 4 weeks, the expression and intracellular storage levels of gonadotropins remained highly suppressed, judging from the labeling density for LHbeta. These findings suggest that the depot formulation of the GnRH agonist could suppress both the biosynthesis and release of gonadotropins for a month by synergistically depleting the intracellular storage of secretory granules at the onset of the treatment and by inducing the subsequent desensitization of the GnRH receptor signaling.
- Subjects :
- Agonist
Male
endocrine system
medicine.medical_specialty
Histology
旭川医科大学:博士(医学)(甲第360号)
Depot
medicine.drug_class
Fluoroimmunoassay
Gonadotrophs
Gonadotropic cell
Gonadotropin-Releasing Hormone
Desensitization (telecommunications)
Leuprorelin
Pituitary Gland, Anterior
Internal medicine
Testis
medicine
Animals
学位授与年月日:平成18年6月30日
Rats, Wistar
biology
Chromogranin A
Fertility Agents, Female
Luteinizing Hormone, beta Subunit
Organ Size
Rats
Rat Pituitary
Endocrinology
Secretogranin II
Delayed-Action Preparations
biology.protein
Ultrastructure
Leuprolide
hormones, hormone substitutes, and hormone antagonists
medicine.drug
Subjects
Details
- ISSN :
- 09149465
- Volume :
- 70
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Archives of histology and cytology
- Accession number :
- edsair.doi.dedup.....f4680f449709c041d3b7425e94bd80fb