The hypocholesterolemic and anti-atherosclerotic mechanism by which soy may exert a beneficial effect remains unclear. Peroxisome-proliferator activated receptors (PPAR) are promiscuous nuclear receptors that regulate the transcription of genes involved in lipid and glucose homeostasis and lipid metabolism within the cell. We hypothesize that the isoflavones improve lipid and glucose metabolism by acting as an antidiabetic PPAR agonist. Male and female obese Zucker rats (OZR) were used as a model of Type 2 diabetes, and OZR fed a high isoflavone soy protein diet displayed improvements in lipid metabolism consistent with results in humans treated with antidiabetic PPAR agonists such as the fibrates or glitazones. Liver triglyceride and cholesterol concentrations were lower in all OZR fed high-isoflavone soy protein diets than in rats fed low-isoflavone and casein diets (P < 0.05). Concurrently, PPAR-directed gene expression was evaluated in a cell culture model. An isoflavone-containing soy extract doubled PPAR-directed gene expression (P < 0.05) in RAW 264.7 cells containing either a PPARalpha or PPARgamma expression plasmid. A similar induction was observed when the soy isoflavones genistein or daidzein were used to treat cells. Both isoflavones doubled PPARalpha-directed gene expression (P < 0.05), whereas they increased PPARgamma-directed gene expression 200-400% (P < 0.05). This study suggests that soy isoflavones improve lipid metabolism, produce an antidiabetic effect, and activate PPAR receptors.

Pulsatile release of GH was compared in young (4-5 months old) and old (18-20 months old) male Sprague-Dawley rats using indwelling atrial cannulae. More than 57% of the young rats exhibited GH pulses greater than 300 ng/ml plasma, whereas only 7% of the old animals had GH pulses of similar amplitude. Trough GH values were not different between young and old rats, but during the 10.5-h sampling period, mean GH concentrations in young male rats were significantly greater than those in old male rats (175.3 +/- 20.9 vs. 70.2 +/- 7.6 ng/ml; P < 0.01). In another experiment, pituitary GH and hypothalamic somatostatin content were measured in young and old rats. The pituitary GH content was significantly greater in young than in old males (1187 +/- 95 vs. 670 +/- 93 microgram; P < 0.01). The immunoreactive somatostatin content in caudal areas of the hypothalamus was also greater in young than in old male rats (100.2 +/- 4.2 vs. 79.0 +/- 5.1 ng; P < 0.01). These observations demonstrate that GH secretion is depressed in old male rats, and this is associated with diminished pulsatile release of GH. The results also suggest that a relationship exists among the reduction in somatostatin content, pituitary GH content, and attenuated GH secretion in old male rats.

Serum estradiol, progesterone, LH, and FSH were determined by RIA in 20- to 30-month-old constant estrous (CE), irregular pseudopregnant (PP), and anestrous (AS) female rats and from 4- to 5-month-old cycling female rats. Disruption of the estrous cycle in aging rats was associated with major changes in secretion of pituitary gonadotropins and ovarian steroids. None of the old rats, in contrast to the young rats, showed cyclic changes in any of the hormones studied. Serum progesterone was much higher in the PP than in the other two old groups, serum estradiol averaged somewhat higher in the CE than in the other two aged groups, and all four hormones were lower in the AS rats than in any other group. Basal serum FSH values were higher in the old CE rats than in either of the other old age groups and were slightly higher than in young rats on the afternoon of proestrus or morning of estrus. Serum FSH values were lower in the old PP and AS rats than in young rats on the afternoon of proestrus or morning of estrus. Serum FSH values were lower in the old PP and AS rats than in young rats on the afternoon of proestrus or morning of estrus. Serum values in the old CE rats were about the same as in young rats on the morning of proestrus or estrus, about the same in old PP rats as in young rats during diestrus, and were undectable in old AS rats. Since the ovaries of old rats are capable of near normal function under appropriate gonadotropic stimulation, it is concluded that the major cause for cessation of regular estrous cycles in old rats lies in altered hypothalamo-pituitary function.

No abstract

No abstract

The effects of streptozotocin-induced (STZ) diabetes on neuroendocrine and sexual function were evaluated in adult male rats. Adult male rats were injected with STZ (50 mg/kg) or vehicle and tested for copulatory behavior 7, 14, and 21 days later. The rats were killed 1 month after STZ or vehicle treatment for measurement of plasma hormone levels, hypothalamic catecholamine turnover, LHRH content, and in vitro pituitary function. The STZ rats showed significant deficits in mount, intromission, and ejaculatory behaviors. Plasma levels of testosterone, LH, FSH, and PRL were all significantly reduced in the STZ compared to the control rats, but in vitro LH secretion was enhanced after STZ treatment. In vitro PRL secretion and the inhibitory response to dopamine did not differ between the two groups. The levels of LHRH were reduced in the medial basal hypothalamus (MBH), but LHRH levels in the median eminence (ME) and anterior hypothalamus (AH) were unchanged after STZ treatment. Norepinephrine turnover was reduced in the ME, MBH, and AH of the STZ rats, while dopamine turnover was unchanged in the ME, increased in the MBH, and reduced in the AH of the STZ rats compared to those in the vehicle-treated controls. These results suggest that changes in pituitary and testicular function in rats made diabetic by STZ treatment are secondary to changes in hypothalamic catecholamine metabolism. Changes in copulatory behavior could be due to both reductions in plasma testosterone levels as well as changes in central neurotransmitter metabolism.

This study details the procedures involved in measuring a number of the componets of indole metabolism within the pineal gland. Tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid, N-acetyltransferase (NAT) activity, and hydroxyindole-O-methyltransferase activity were measured by a combination of three techniques, which included microassays, radioimmunoassay, and high-performance liquid chromatography. Determination of the melatonin synthetic pathway components within the same gland reduces the number of animals needed for studies and allows correlations between these constituents to be calculated. Very high degrees of correlation (r = 0.91-0.99) are seen between those compounds which exhibit significant rhythms (serotonin, NAT activity, N-acetylserotonin, and melatonin) when group means are compared. When correlations are calculated on a per-animal basis throughout the experiment, moderate to high degrees of correlation (r = 0.57-0.79) are found among those components that exhibit rhythms. However, when correlations are determined on a per-animal basis at each time point, no significant correlations are found. One hypothesis accounting for these differences may be that changes occur in indole metabolism within the same pineal gland over a period of a few minutes.

The adverse effects of diabetes on the circulatory, visual, renal, and peripheral nervous system are commonly recognized and have been extensively studied. The effects of decreased insulin secretion or resistance to insulin action on endocrine glands have not been as carefully documented. Both clinical and animal research have demonstrated that diabetes mellitus is commonly associated with altered thyroid, adrenal and gonadal function. Some of these changes are reversed with insulin replacement therapy, but endocrine function is not always restored to normal even with rigorous glycemic control. Patients with poorly controlled diabetes exhibit basal and stimulated growth hormone (GH) hypersecretion, while patients with good metabolic control still present with diurnal and exercise-induced GH hypersecretion. In contrast, diabetes suppresses GH secretion in the rat. It is unclear why GH secretion is altered, but clinical and experimental evidence exists for diabetes-associated changes in GH-releasing hormone and somatostatin release as well as for changes in the pituitary response to these hypothalamic hormones. The thyroid hormones, T3 and T4, are usually suppressed in both humans and experimental animals with diabetes. This effect of diabetes appears to involve changes in hypothalamic thyrotropin-releasing hormone (TRH) secretion as well as changes in pituitary thyrotropin (TSH) release and direct effects at the level of the thyroid gland. Adrenal cortical function is often enhanced in diabetes, most likely due to alterations in glucocorticoid feedback responses. There is much conflicting data on adrenal medullary function in diabetes; responses to stress and exercise, however, are often abnormal. Finally, male and female reproductive function is often disrupted in diabetes. Data from animal studies suggest that the major cause is altered hypothalamic LHRH secretion secondary to diabetes-induced changes in hypothalamic neurotransmitter metabolism.