Effects of hyperprolactinemia on toxicological parameters and proliferation of islet cells in male rats

Abstract

INTRODUCTIONHyperprolactinemia is a common clinical disorder due to long-term administration of chemicals such as dopamine D2 receptor antagonists. The role of toxicological evaluation is to protect humans from toxicity induced by drugs or other chemicals and unwanted side effects. It is necessary to assess and differentiate direct toxicological effects of compounds from their secondary effects.The anterior pituitary-grafted rat is well known as a useful model animal for research on hyperprolactinemia; many of which focused on hormonal changes, body weight or glucose metabolism (Matsuda et al., 1994;Reis et al., 1997;Adler, 1986) by means of this model although they had only patchy information. On the other hand, in females, physiological hyperprolactinemia is observed during pregnancy and the subsequent post partum lactation period. Many studies have revealed that prolactin (PRL) is mainly characterized by increases in insulin secretion and islet cell mass in vivo and in vitro and is closely related to glucose (GLU) metabolism in females et al., 1993;Parsons et al., 1995). However, there is lack of information in males especially regarding the effects of hyperprolactinemia on toxicological parameters.The present study was designed to clarify the effects of hyperprolactinemia on toxicological parameters using anterior pituitary-grafted male rats. The study took into account sex difference of donors since PRL contents and the proportion of lactotrophs in female rat-derived anterior pituitary grafts are greater than those in their counterparts derived from male rats (McArthur et al., 2006). Also, the study included the effects of hyperprolactinemia on islet cell proliferation in male rats because sever- ABSTRACT -Prolactin has a wide variety of biological effects. Consequences of hyperprolactinemia on islet B cell proliferation as well as general toxicological parameters were here examined using anterior pituitary-grafted rats. Three or six anterior pituitary glands were implanted under single renal capsules of F344 male rats and left there for 13 weeks afterward. Clinical observation along with measurement of body weight and food consumption was conducted during the observation period, and subsequently hematology, blood biochemistry, gross pathology, organ weights and histopathology were examined. In addition, the proliferation rate of islet B cells was measured by a 5-bromo-2'-deoxy-uridine (BrdU) labeling technique. Serum prolactin concentrations at week 13 were 36, 70, 75 and 105 ng/ml in the shamoperated, 3-pituitary-grafted groups from male or female donors, and 6-pituitary-grafted group from male donors, respectively. Higher cholinesterase and total cholesterol values, lower trigriceride and leutenizing hormones (LH) values, and higher adrenal weights compared to those in the sham-operated group were apparent in the 3-and/or 6-pituitary-grafted groups. Also, the study revealed that mammary gland structure was transformed with change of differentiation from a male to a female acinar pattern. Furthermore a -...

Proliferative and Nonproliferative Lesions of the Rat and Mouse Mammary, Zymbal’s, Preputial, and Clitoral Glands

“…rats: If due to effects of PRL, tubular profiles are more frequent and alveolar profiles are lined by smaller, cuboidal cells with basophilic cytoplasm; alveoli have a thinned epithelium Male rats or mice: humans. In male rats, xenobiotics that increase PRL will result in atrophy of alveoli resulting in a tubulo-alveolar appearance of the gland similar to what is observed in the normal virgin female gland (Figure15;Ose et al 2009;Lucas et al 2007). In both males and females, xenobiotics may perturb the hypothalamic-pituitary-gonadal axis resulting in a decrease in circulating, mammotrophic hormones resulting in glandular atrophy.…”

Early weaning causes undernutrition for a short period and programmes some metabolic syndrome components and leptin resistance in adult rat offspring

“…Changes in glucose homeostasis in adult life, such as lower insulin secretion ( 59 , 60 ) , changes in insulin sensitivity ( 12 , 61 ) , higher glucogenolysis ( 62 ) , lower β-cell quantity and pancreatic content of insulin ( 63 ) are associated with protein malnutrition in critical periods of life. Moreover, PRL modulates the proliferation of pancreatic β-cells and the consequent lowering of glycaemia ( 64 ) . The fact that programmed EW rats had lower serum PRL could explain why they have an inappropriate response of insulin to hyperglycaemia have shown were adults, perhaps because they have an impairment on the development of pancreatic β-cells, Recently, we have shown that maternal hypoprolactinaemia for the last 3 d of lactation programmes for insulin resistance and lower serum PRL in their adult offspring ( 22 ) .…”

Maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny

“…Thus, it is possible that hyperglycaemia and failure of insulin to respond adequately, found in our present study, may be due to higher body fat. Several studies showed an important role of PRL on the proliferation of pancreatic beta cells (Cunha et al 2007; Huang et al 2009) and consequent lowering of glycaemia (Ose et al 2009). The fact that our programmed animals had lower PRL serum levels when adults, could explain why they have an inappropriate response of insulin to hyperglycaemia when adults, maybe because they have an impairment in the development of pancreatic beta cells.…”