Abstract. Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 µl phosphate buffered saline with or without 1 µg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p < 0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p < 0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p < 0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic disbalance effects, remains a very important research goal.

Abstract. The long-term effects of somatostatin 14 (SST-14) on the pituitary-ovarian axis were examined. Female Wistar rats received 20 µg/100 g b.w. doses subcutaneously twice daily for 5 consecutive days in the infantile (from 11 th to 15 th day) or peripubertal (from 33 rd to 37 th day) period of life. Females treated as infants were killed in the peripubertal (38 th day) or adult period of life (80 th day), and those treated during peripuberty as adults (80 th day). Pituitary follicle-stimulating (FSH), luteinizing (LH) and somatotropic (GH) cells, and ovaries were analyzed by stereology and morphometry. Serum FSH and LH concentrations were determined by RIA. FSH and LH cell volumes were significantly decreased in pituitaries of peripubertal females treated with SST-14 as infants, and in adult females treated during peripuberty. GH cell volume was decreased in all treated rats. In the ovaries, enlargement of the non-growing pool of follicles was detected in adult females treated during peripuberty. SST-14 applied to infant rats did not lead to changes in initial follicular recruitment, but it disturbed follicle growth and development at later stages. It can be concluded that SST-14 exerted long-term inhibitory effects on the pituitary-ovarian axis and GH cells in rats.

Abstract. The soybean phytoestrogen, genistein, is increasingly consumed as an alternative therapeutic for age-related diseases. The aim of this study was to examine the morphofunctional characteristics of adrenocorticotrophic (ACTH) cells and blood concentrations of ACTH in sham-operated, orchidectomized and genistein-treated orchidectomized, 16-month-old Wistar male rats. Genistein (10 mg/kg/day) was administered subcutaneously for three weeks, while the control groups received the vehicle alone. Orchidectomy and genistein treatment decreased the volume density of ACTH cells and reduced (p < 0.05) circulating ACTH concentrations in comparison with control groups. In conclusion, genistein modulated the morphofunctional features of ACTH cells and decreased blood ACTH levels.Key words: ACTH -Genistein -Middle-age -Orchidectomy -Rats * These authors contributed equally to the paper. Correspondence to: Verica Milošević, Institute for Biological Research "Siniša Stanković", 142 Despot Stefan Blvd., 11060 Belgrade, Serbia E-mail: dimi@ibiss.bg.ac.yu Some plant derived compounds, structurally similar to endogenous mammalian hormones, can mimic or antagonize the actions of these hormones and, thereby, affect certain events controlled by the endocrine system (Adlercreutz and Mazur 1997). Genistein, an isoflavone from soybeans, has structural and functional similarity to 17β-estradiol (Setchell 1998) and acts as a phytoestrogen. It has significantly higher affinity for estrogen receptor β than for estrogen receptor α (Kuiper et al. 1997). Genistein is also well known as a tyrosine kinase inhibitor (Akiyama et al. 1987). Nutritional supplements containing genistein are widely used as an alternative therapy for cardiovascular diseases, osteoporosis and cancer by people of advanced age. Data illustrating the effects of genistein on adrenocorticotrophic (ACTH) cells are rather scarce. It is known that various cytokines are involved in the regulation of ACTH secretion and that some synergism exists between cytokines and corticotrophin releasing hormone on stimulation of proopiomelanocortin (POMC) gene expression (Besedovsky and del Rey 1996;Katahira et al. 1998). As a potent tyrosine kinase inhibitor, genistein interrupts the tyrosine phosphorylation cascade and inhibits stimulatory effects of cytokines on POMC gene transcription in vitro (Katahira et al. 1998). The present study was designed to evaluate the effects of subcutaneously applied genistein in a small therapeutic dose on morphometric and functional characteristics of ACTH cells in the pituitary gland of orchidectomized middle-aged male rats (animal model of the andropause). Orchidectomy was carried out with a view to annihilate the effects of endogenous sex steroids on the anterior pituitary.The experiments involved 16-month-old male Wistar rats, which were bred in the Institute for Biological Research (Belgrade, Serbia), housed two per cage, exposed to a 12 : 12 h light/dark cycle and kept at 22 ± 2ºC. Two weeks before the experiment, the rats started to eat a soy...

Abstract. Ghrelin, the endogenous ligand of growth hormone secretagogue receptor type 1a (GHS-R1a), has emerged as pleiotropic modulator of diverse biological functions, including energy homeostasis and recently, reproduction. The influence of intracerebroventricularly (ICV) administered ghrelin (1 μg/day/rat for 5 days) to rats of different ages, i.e., peripubertal (38 days), adult (60 days) and middle-aged (180 days) on the ventral prostate size and morphology, serum testosterone levels and testis weight was examined. Ghrelin treatment significantly increased (p < 0.05) absolute ventral prostate weight in peripubertal and middle-aged rats, by 27% and 37% respectively, due to enhancement of epithelial and/or luminal compartment of the gland. In adult rats, both absolute and relative volumes of the acinar lumen were significantly decreased (p < 0.05), by 38% and 44% respectively, which was associated with significant increases (p < 0.05) in relative and absolute volumes of interacinar stroma, whereas ventral prostate weigh was unchanged. Irrespective of animal age, ghrelin did not affect serum testosterone levels. These are the first results of ghrelin treatment effects on healthy prostate appearance, which allow us to conclude that the rat ventral prostate response to ghrelin depends on the developmental stage of animals. Our results merit further investigations and may have clinical implications, especially in the light of data on possible role of ghrelin in prostate hypertrophy and adenomas.

Abstract. In peripubertal female rats, we have previously found that 50% food restriction (FR) increases plasma IL-6, haptoglobin and both alanine transaminase (ALT) and alkaline phosphatase (AST) aminotransferases, indicating the existence of an inflammatory response. To study whether such FR influences the hypothalamic-pituitary-adrenal (HPA) axis, we examined by immunohistochemistry the morphofunctional features of pituitary adrenocorticotropic (ACTH) cells. In FR rats the volume and volume density of ACTH cells as well as plasma ACTH levels were increased by 17.6%, 12.5% and 13.4%, respectively, in comparison with controls (p < 0.05). We concluded that chronic FR is a systemic stressor in young females, capable to stimulate the HPA axis, probably as a result of IL-6 action.