Search

A specific and sensitive homologous radioimmunoassay (RIA) for determination of hamster prolactin is described and compared to heterologous hamster prolactin RIA and to the homologous and heterologous RIAs for rat prolactin. With this method, we have determined that, in the golden hamster, diurnal plasma prolactin fluctuations have a mean interpeak interval of 1.5 h, that serum prolactin concentrations are influenced by day length, by ether vapors, by animal's gender, and by refeeding following a fast but not by neurosurgical procedures which increase somatic growth and serum GH concentration in adult hamsters. Variations in day length influenced pituitary prolactin content and concentration, and pituitary removal abolished prolactin secretory responses to ether stress. A heterologous RIA for hamster prolactin which utilizes radioiodinated rat prolactin and rabbit antihamster prolactin serum (RK1-15) represents the most advantageous method for the measurement of hamster prolactin because of its high sensitivity (0.14 ng/ml), high antiserum binding to iodinated rat prolactin, and the ability to measure both hamster and rat prolactin.

Exercise accelerates somatic and skeletal growth in mature nondeprived hamsters and induces catch-up growth when food restriction during exercise is followed by ad libitum realimentation. The hypothesis that nutrient availability controls the rate of growth through changes in anabolic hormone release was tested through measurements of serum growth hormone (GH) and insulin concentrations at the same time of day in exercising and sedentary hamsters subjected to acute fasts, chronic food restriction, and to acute and prolonged realimentation. Concentrations of GH and insulin increased in ad libitum-fed exercising hamsters, but these increases were abolished by 12 and 4 h of fast, and restored by 4 and 2 h of refeeding, respectively. Four h of refeeding restored exercise-induced increases in serum GH, but not in serum insulin concentration in chronically food-restricted hamsters. During catch-up growth, the growth rate was double that of ad libitum fed exercising hamsters, but the increases in serum GH concentration in the two situations were similar. I conclude that increases in serum GH rather than in serum insulin concentration are the most probable determinant of exercise-induced growth and catch-up growth because they are relatively refractory to short-term nutritional perturbations.

Limbic forebrain inhibits growth and growth hormone (GH) secretion in mature golden hamsters as shown by acceleration of growth and increases in serum GH concentrations following the electrolytic lesions of septum, transection of the hippocampus and surgical separation of these two regions. The growth-inhibitory function of this circuit is most probably mediated by somatostatinergic (SRIF) neurons. Such lesions induce hypoactivity possibly due to damage to endogenous opiatergic (EOP) neurons. EOP neurons facilitate spontaneous running in hamsters and mediate exercise-induced acceleration of growth and GH pulses. The coincidence of hypoactivity and growth acceleration after such lesions suggested the coexistence of SRIF and EOP fibers within the growth-inhibitory limbic forebrain circuit which control the rate of growth in mature hamsters by the variable inhibition of SRIF neurons by the EOP neurons. This hypothesis posits that accelerated growth is due to increased GH pulse frequency, and hypoactivity due to damage to EOP neurons, and was tested in this study by measuring pulsatile GH release (and as a measure of specificity, pulsatile prolactin release) in the presence and in the absence of opiate-receptor blocker naloxone in 21 female hamsters which sustained electrocoagulative lesions of rostromedial septum and 30 hamsters subjected to control surgery. Lesions doubled GH but not PRL pulse frequency, neither of which was affected by naloxone. Results support the hypothesis that opiatergic neurons facilitate pulsatile GH release by inhibiting the action of somatostatin neurons.

In contrast to the inhibitory effects of endurance exercise on reproductive function in women athletes, voluntary running induces estrous cyclicity in anestrous female hamsters maintained in the nonstimulatory short-day photoperiod. Increased concentrations of circulating prolactin (Prl) seen in these animals are not responsible for the reversal of photoperiodic anestrus as demonstrated by experimental manipulations of prolactin secretion. Voluntary running also facilitates growth hormone (GH) release and somatic growth in hamsters independently of the photoperiod. Thus, it appears that endurance exercise can have facilitatory as well as inhibitory effects on the reproductive function in female mammals.

Naltrexone HCl, a long-acting opiate receptor blocker was administered to female hamsters at two doses, 10 and 20 mg/kg, IP prior to 12 hr of nocturnal running or every 12 hr during access to hypothalamic self-stimulation to determine whether endogenous opiates played a role in either of these two motivated behaviors. Naltrexone suppressed total running activity and speed, and caused an increase in pause time but did not affect the rate of hypothalamic self-stimulation. Furthermore, weight gain was unaffected by four weeks of self-stimulation but was accelerated during two weeks of voluntary running. Thus stimulation of endogenous opiate receptors helps support high levels of voluntary running but is not involved in initiation of running or in maintenance of intracranial self-stimulation in female hamsters. Furthermore, the association of opiate receptor stimulation and increased somatic growth with voluntary running but not with self-stimulation suggests a possible facilitatory role for endogenous opiates in acceleration of growth by exercise.

Somatic, endocrine and behavioral correlates of growth were measured in intact and hypophysectomized adult hamsters with or without electrolytic damage to the rostral septal area. Septal (SEP) lesions significantly increased somatic growth rate, food consumption and serum concentration of growth hormone (GH) and insulin. Pituitary GH content and concentration were reduced in lesioned hamsters. None of these changes were found in hypophysectomized hamsters with SEP lesions. SEP lesions did not affect the percentage of body fat. These data suggest that the septum or adjacent fibers of passage inhibit growth in adult hamsters.

Senescent hamsters display a marked reduction in volume of voluntary running. The purpose of this study was to determine whether age differences exist in the pattern of fuel utilization during submaximal exercise, which may account for the reduction in voluntary running. Further, we determined the effects of age on muscle oxidative capacity to assess its relationship to endurance performance in senescent hamsters. Depletion of carbohydrate and lipid content of skeletal muscle and liver, and changes in blood concentration of various hormones and substrates during one hour of exercise at 60 percent of VO2 max served to assess age effects on utilization of metabolic substrates. Exercise produced equivalent depletion of muscle glycogen and similar rise in plasma free fatty acids in young and old hamsters. No exercise effects on skeletal muscle triglyceride concentration or on plasma glycerol, glucagon or catecholamine concentrations were noted. With palmitoyl carnitine as substrate (but not with pyruvate) State 3 respiration of cardiac and skeletal muscle homogenates was lower in old compared to young hamsters. Although old hamsters have a reduced capacity to oxidize lipids in vitro, few age differences in fuel use are evident in vivo during submaximal exercise. Thus, these minor age differences in substrate utilization do not likely account for the substantial reduction in the levels of spontaneous running in senescent hamsters.

The pattern of hypoactivity that accompanies rapid weight gain following septal lesions in hamsters was characterized. Lesioned hamsters displayed reduced levels of running, shorter and slower running bouts, and longer pauses. We examined whether this hypoactivity was due to reassignment of metabolic fuels from supporting physical activity to anabolism, or due to reduced capacity of running to induce psychomotor arousal and mobilize metabolic fuels. Septal lesions were associated with increased rate of ponderal growth and higher titers of circulating growth hormone and insulin. No difference in concentrations of muscle and liver glycogen, percentage of body fat, or the capacity of muscle homogenates to oxidize substrates were identified. Lesioned hamsters ran as fast and as long as control animals on electrical-shock reinforced treadmill, but were unable to generate as much heat in response to injection (0.8 mg/kg) of norepinephrine. We concluded that hypoactivity that accompanies rapid weight gain in hamsters results either from a reduced capacity of running to induce psychomotor arousal and provide incentives that normally motivate that behavior, or from a failure of running to mobilize metabolic fuels at a rate necessary to sustain normal running speed and duration, and not from reduced availability of metabolic fuels or reduced muscle capacity to oxidize metabolic substrates.

Syrian golden hamsters when allowed free access to food and an exercise wheel will run long distances and develop hyperphagia and accelerated linear body growth with high circulating levels of growth hormone and insulin. Somatostatin, a widely distributed brain-gut neurohormonal peptide, modulates nutrient absorption and may regulate food intake. To examine the role of circulating plasma somatostatin-like immunoreactivity (SRIF-LI; pg/ml) in exercise induced hyperphagia 4 groups of animals were studied; an unrestricted exercise group (279.0 +/- 107.7, n = 10); a sedentary group (121.1 +/- 40.8, n = 8); a restricted exercise group (107.7 +/- 12.4, n = 6); and a restricted no exercise group (115.5 +/- 45.9, n = 9). Thus, the unrestricted exercise group has a significantly elevated SRIF-LI concentration (P less than 0.01) while there was no difference between the other 3 groups. The elevation of plasma SRIF-LI in the unrestricted exercise group may represent a response to modulate increased nutrient entry in this group or may represent an incompletely effective satiety signal.

To determine whether endogenous opiates mediate hyperactivity in food restricted hamsters and serotonergic fibers innervating the hippocampus mediate hypoactivity in obese hamsters, food restriction and high-fat diet supplementation were used to produce significant body fat changes (8 vs. 21%). The levels and pattern of spontaneous running were examined after IP saline or naloxone HCl (20 mg/kg) and following the infusion of vehicle and 5,7-dihydroxytryptamine creatine sulfate (4 micrograms/2 microliters) into rostromedial septum of mature female hamsters. Septum-medial preoptic area (POA), hippocampus, hypothalamus, and cortex were dissected from the three groups as well as from two additional groups of hamsters receiving vehicle or neurotoxin. Concentrations of serotonin, norepinephrine, and dopamine were measured in these tissues by HPLC method. Fat-fed hamsters were hypoactive relative to food-restricted hamsters. Naloxone had no significant effect on running behavior. Serotonin neurotoxin increased the running activity of fat-fed hamsters to the level displayed by control hamsters by increasing the number of runs, the total activity level, the speed of running and by decreasing the duration of pauses. Neurotoxin led to selective deletion of serotonin in the hippocampus (77%) and parietal cortex (50%). Serotonergic fibers innervating the hippocampus thus appear to mediate the hypoactivity that is induced by dietary obesity in mature hamsters. Since serotonin mediates some other manifestations of aging, and slow weight increases characterize mid-portion of hamster life span, we hypothesize that serotonergic mediation of hypoactivity is another manifestation of aging.

A heterologous radioimmunoassay (RIA) for determination of hamster growth hormone (GH) is described which involves the use of radioiodinated rat GH (NIAMDD Rat GH-I-2), antiserum to rat GH (NIAMDD Anti-Rat-GHS-3), a standard hamster anterior pituitary homogenate (SHAP), as well as purified hamster GH (AFP-1595-B). This RIA was shown to be a reliable, sensitive, and specific method for measurement of hamster GH. With this method we have determined the effects of stress and hypophysectomy on serum GH concentrations as well as changes in serum GH concentration, and pituitary GH content and concentration as a function of hamster age. In contrast to responses noted in rats, the stress of ether anesthesia and i.c. puncture caused significant increases in serum GH. A decrease in the serum GH concentration was observed in hamsters at the age 2 to 16 days. Pituitary GH content and concentration increased steadily between 9 and 120 days of age.

Voluntary exercise permanently elevates body weight in adult hamsters (Borer, K.T. Physiol. Behav. 12:589, 1974). Possible effects of such exercise on skeletal growth were examined in female hamsters in the asymptotic phase of growth, 14 of which had a 34-day access to horizontal disc exercisers, while 14 others remained sedentary. Skeletal measurements were taken from radiographs obtained at the start and at the end of exercise and on day 29 of retirement. Exercise was associated with more pronounced growth of axial than appendicular skeleton. Vertebral column, skull, humerous and femur of excercising hamsters grew 5.61 +/- 0.75 (p less than .001), 1.26 +/- 0.49 (p less than .05), 1.96 +/- 0.81 (p less than .02) and 2.80+/-1.34 (p less than .05) percent more, respectively, than the corresponding bones of sedentary hamsters. Appendicular skeleton continued to grow during retirement. Humerus and femur grew 1.96+/-0.65 (p less than .02) and 1.67+/-0.59 (p less than .02)% more, respectively, during retirement in exercised than in sedentary hamsters. Significantly greater weight gain was seen in active than in sedentary hamsters during both exercise (25.62 + 2.68%, p less than .001) and retirement (6.43 + 2.23, p less than .02). These data indicate that disc exercise accelerates skeletal and ponderal growth in adult hamsters and that axial and appendicular skeleton respond to this stimulus differently.

Our aim was to examine whether 1) growth-inducing exercise altered the pulsatile pattern of GH release, 2) endogenous opiates mediated these changes, and 3) endogenous somatostatin (SRIF) suppressed pulsatile GH secretion in slowly growing sedentary hamsters. To that end, mature female hamsters were either exposed to 2 weeks of voluntary running or prevented from engaging in running activity. Intracardiac catheters were inserted to allow blood collection every 20 min during 6 h. GH and PRL secretory patterns were determined with homologous RIAs for hamster hormones after administration of saline, naloxone, or anti-SRIF serum. It was found that exercise accelerated somatic growth. GH pulse frequency and amplitude were significantly higher in rapidly growing hamsters. The rate of growth was inversely related to basal trough values of GH and PRL. Opiate receptor blockade reduced GH pulse frequency and amplitude to below sedentary values and did not affect PRL secretion. Anti-SRIF serum increased GH pulse frequency and amplitude in naloxone- as well as in saline-injected animals. Our results are consistent with the conclusions that 1) rapid growth, spontaneous or induced by exercise, is associated with increased GH pulse frequency and amplitude and decreased GH and PRL baseline concentrations in hamsters; 2) endogenous SRIF inhibits pulsatile GH secretion in slowly growing hamsters; and 3) endogenous opiates mediate increases in GH pulse frequency and amplitude in rapidly growing hamsters by antagonizing the endogenous SRIF action.

Concentrations of somatostatin-like immunoreactivity (SRIF-LI) were measured in cerebral cortex, hippocampus, septum-POA, median eminence, gastric antrum, fundus and pancreas in adult female hamsters to determine whether changes in somatostatin could be related to increased growth hormone (GH) secretion and somatic growth that follow bilateral transections of hippocampus (n = 18; 17 controls). In addition, choline acetyltransferase (CAT) activity was measured in the four brain regions in hippocampectomized (n = 10) and control hamsters (n = 10) to gain insight into the relationship between these two neurotransmitters. Hippocampal transections induced: significant acceleration of somatic growth; increased serum GH concentrations; increased concentrations of SRIF-LI in septum-POA and gastric antrum; reduced concentrations of SRIF-LI in hippocampus and pancreas; and reduced CAT activity in the hippocampus. These results suggest that somatostatinergic and cholinergic projections to hippocampus via fornix suppress GH and somatic growth in adult hamsters and that reduced release of SRIF-LI in the gastric antrum may contribute to the acceleration of somatic growth through facilitated nutrient digestion and entry.

The effects of daily evening melatonin injections on serum and pituitary levels of growth hormone (GH) and follicle stimulating hormone (FSH) were investigated in male Syrian hamsters receiving thiourea in the drinking water. Melatonin injections, by themselves, had no significant effect on serum or pituitary GH. Thiourea induced hypothyroidism reduced pituitary GH content but increased serum GH several fold. Daily thyroxin (T4) injections for 3 weeks partially restored pituitary GH content and reduced circulating GH to control values. Melatonin injections prevented T4 from reducing circulating GH levels to normal in hamsters receiving thiourea. As previously reported, FSH levels in serum and pituitary were reduced by melatonin. Thiourea-induced hypothyroidism prevented this effect. Daily T4 injections increased circulating FSH levels above control levels; melatonin injections prevented this increase in serum FSH. These observations show that melatonin and T4 have antagonistic actions on GH and FSH release from the pituitary. We conclude that melatonin influences the release of hypothalamic hormones regulating GH and FSH release from the pituitary. The effects of T4 on the sensitivity to melatonin injections could be accounted for by thyroid hormone regulation of pituitary receptors for hypothalamic hormones. An alternative explanation is that T4 regulates the concentration of melatonin receptors in the central nervous system.

Rostral septal lesions accelerate somatic growth in adult hamsters. This study tested the hypothesis that this effect results from damage to fibers of passage by observing the effects of transections of septohippocampal and septohypothalamic connections on growth. We attempted to identify these fibers further by (a) measuring spectrofluorometrically changes in the monoamine concentrations in hippocampus, cerebral cortex, corpus striatum, and diencephalon, (b) staining the degenerating axons after septal lesions and the two cuts, and (c) examining the correspondence between such damage and the acceleration of growth. Both knife cuts accelerated somatic growth and were associated (as well as septal lesions) with significant depletions of serotonin (-27 to -57%) and norepinephrine (-27 to -60%) in the hippocampus, with less consistent depletions of these monoamines in the cerebral cortex, and with no changes in regional dopamine content. All three procedures were associated with degeneration in the hippocampal formation and its fiber systems. Thus, fibers interconnecting hippocampus and brainstem, and passing through septum, exert tonic suppression over somatic growth in adult hamsters.

The mechanism responsible for weight stability in adult hamsters was investigated by (a) transecting the dorsoventrally oriented nerve pathways between the septal area and hypothalamus (SH cuts) and (b) partitioning the observed increases in the rate of weight gain into three contributory components: changes in somatic growth, in body fatness, and in energy expended as voluntary activity on horizontal disks. Between 60% and 70% of the weight increase after SH cuts was due to acquisition of lean body mass, and 30%-40% of weight increase consisted of excess body fat. After SH cuts, serum growth hormone and insulin concentrations were increased on Day 14, food intake was increased between Day 2 and Day 42, skeletal lengths were greater on Day 77, and voluntary activity levels were 84% lower on Days 10-45, relative to control hamsters. It is concluded that dorsoventrally oriented nerve pathways in the septal area are involved in the control of growth, maintenance of body fat reserves, and voluntary activity and that they contribute to the maintenance of stable body weight in adult hamsters.