Effect of drugs on pituitary ultrastructure

Abstract

Various drugs and hormones influence the light microscopic and especially the electron microscopic structure of the anterior pituitary and its tumors. Many structural effects are known only from animal experiments since specimens from human pituitaries are mostly not available. The structure of growth hormone (GH) cells is relatively stable. A massive GH cell hyperplasia is known only in rare cases with growth hormone releasing factor (GRF) excess from tumors. Prolactin cells can be stimulated by drugs, neurotransmitters, and hormones which decrease the dopamine inhibition. Adrenocorticotropic hormone (ACTH) cells are stimulated by stress, some hormones, loss of adrenals, and drugs which activate the alpha 1- and beta-receptors or inhibit the alpha 2-receptors. They are suppressed and changed into Crooke's cells by treatment with glucocorticoids. Thyroid-stimulating hormone (TSH) cells increase in number and size in states for overstimulation especially by thyrotropin releasing hormone (TRH). A decrease results from hyperthyroidism and possibly from somatostatin, L-dopa, and dopamine. Gonadotroph cells transform into castration cells in strongly hyperactive states (gonadectomy, antiandrogens, gonadotropin releasing hormone [Gn-RH]agonists, aminoglutethimide). Special types of pituitary adenomas can be treated with drugs which suppress hormone production and proliferation. Dopamine agonists and somatostatin reduce the tumor size of varying proportions of GH secreting adenomas in acromegaly. Ultrastructurally, a decrease of cytoplasmic and nuclear volume and an increase of lysosomes are found. Bromocriptine and other dopamine agonists are established in the treatment of prolactin secreting adenomas. They induce a shrinkage in many cases. Ultrastructurally, a reduction of cellular and nuclear size, an increase in number of secretory granules and of lysosomes, and a reduction of rough endoplasmic reticulum can be demonstrated.

Diethylnitrosamine causes pituitary damage, disturbs hormone levels, and reduces sexual dimorphism of certain liver functions in the rat.

“…In the pituitaries from control rats at all time points after DEN administration, most of the granular cells were of the storage type, characterized by many secretory granules and an inactive appearance, with poor development of endoplasmic reticula (ER) and Golgi complex (Figure 1), as described in detail by others (13,37). We observed moderate congestion and hemorrhage under light and electron microscopy in some areas at 1 and 3 days after DEN treatment of male rats (Figure 2 (Figures 2-5).…”

“…The pituitary is refractory to the toxicity of most substances other than hormone analogues or antagonists (13). So far, hexadimethrine bromide has been the only substance shown to cause acute pituitary damage by inducing the rupture of pituitary blood capillaries (39).…”

“…Furthermore, degenerating and dying somatotropes have been reported in the pituitary from rats bearing malignant hepatomas induced by long-term, low-dose treatment of DEN (12). These data raise the question of whether the pituitary, otherwise shown to be refractory to toxic effects of chemicals (13), might be a target for DEN toxicity.…”

Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry

“…Evaluation of the ultrastructure reveals that many adenomas are similar to oncocytic adenomas or null cell adenomas, whereas others show distinct similarities with normal gonadotrope cells. The rough endoplasmic reticulum may be dilated, but the structures of so-called castration cells are not found (73). Secretory granules are sparse and very small.…”

Vias dopaminérgicas e somatostatinérgicas diminuem o TSH sérico em ratos portadores de carcinoma mamário walker-256

“…O uso de análogo da somatostatina (octreotide), empregado no tratamento da acromegalia, acarretou diminuição da concentração plasmática do TSH e da resposta de sua secreção ao estímulo pelo TRH (36,37). Na hipófise, demonstrou-se que o número e o tamanho das células tireotróficas aumentam quando hiper-estimuladas pelo TRH e diminuem no hipertireoidismo, assim como com o estímulo pela somatostatina e dopamina (38).…”