Prevalence of diabetes among children treated with growth hormone in Israel.

AIMS: To determine the long-term risk of diabetes in a cohort of children treated with recombinant human growth hormone in Israel, using data from the Israeli National Diabetes Register. METHODS: Between 1988 and 2009, 2513 children were approved for growth hormone treatment. They were assigned to one of two groups. The first group included children treated for isolated growth hormone deficiency and who were small for gestational age and the second included those treated for multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome or Prader-Willi syndrome. The cohort was cross-linked with the Israeli National Diabetes Register for 2014 (mean follow-up duration 12.1±5.3 years), and prevalent cases of diabetes were identified. Standardized prevalence ratios for diabetes were calculated for people aged 10-29 years. RESULTS: In 2014, a total of 23 individuals were identified with diabetes (four with pre-existing diabetes, seven developed diabetes before age 17 years and 12 developed it at a later age). In the isolated growth hormone deficiency and small-for-gestational-age group there was no difference in the prevalence of diabetes compared with the general population (standardized prevalence ratio 2.05, 95% CI 0.94-3.89). In the group that included people with multiple pituitary hormone deficiency, chronic renal failure, Turner syndrome and Prader-Willi syndrome there was a significantly higher diabetes prevalence (standardized prevalence ratio 11.94, 95% CI 6.53-20.00) compared with the general population. CONCLUSIONS: No difference in diabetes prevalence was found in the isolated growth hormone deficiency and small-for-gestational-age group, compared with the general population. Children treated with growth hormone with pre-existing risk factors had an increased prevalence of diabetes. It is advisable to monitor blood glucose levels closely during and after growth hormone treatment, especially in such children.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics.

A hybrid process of biofiltration of secondary effluent followed by ozonation and short soil aquifer treatment for water reuse.

The Shafdan reclamation project facility (Tel Aviv, Israel) practices soil aquifer treatment (SAT) of secondary effluent with hydraulic retention times (HRTs) of a few months to a year for unrestricted agricultural irrigation. During the SAT, the high oxygen demand (>40 mg L(-1)) of the infiltrated effluent causes anoxic conditions and mobilization of dissolved manganese from the soil. An additional emerging problem is the occurrence of persistent trace organic compounds (TrOCs) in reclaimed water that should be removed prior to reuse. An innovative hybrid process based on biofiltration, ozonation and short SAT with ∼22 d HRT is proposed for treatment of the Shafdan secondary effluent to overcome limitations of the existing system and to reduce the SAT's physical footprint. Besides efficient removal of particulate matter to minimize clogging, coagulation/flocculation and filtration (5-6 m h(-1)) operated with the addition of hydrogen peroxide as an oxygen source efficiently removed dissolved organic carbon (DOC, to 17-22%), ammonium and nitrite. This resulted in reduced effluent oxygen demand during infiltration and oxidant (ozone) demand during ozonation by 23 mg L(-1) and 1.5 mg L(-1), respectively. Ozonation (1.0-1.2 mg O3 mg DOC(-1)) efficiently reduced concentrations of persistent TrOCs and supplied sufficient dissolved oxygen (>30 mg L(-1)) for fully oxic operation of the short SAT with negligible Mn(2+) mobilization (<50 µg L(-1)). Overall, the examined hybrid process provided DOC reduction of 88% to a value of 1.2 mg L(-1), similar to conventional SAT, while improving the removal of TrOCs and efficiently preventing manganese dissolution.

Oxytocin and same-sex social behavior in female meadow voles.

The neuropeptide oxytocin (OT) has been implicated in a range of mammalian reproductive and social behaviors including parent-offspring bonding and partner preference formation between socially monogamous mates. Its role in mediating non-reproductive social relationships in rodents, however, remains largely unexplored. We examined whether OT facilitates same-sex social preferences between female meadow voles-a species that forms social nesting groups in short, winter-like day lengths. In contrast to results from studies of opposite-sex attachment between prairie vole mates, we found that neither OT nor dopamine neurotransmission was required for baseline levels of social partner preference formation or expression. OT enhanced preference formation beyond baseline levels-an effect that was counteracted by treatment with an oxytocin receptor antagonist (OTA). Oxytocin receptor (OTR) density correlated with social behavior in brain regions not known to be associated with opposite-sex affiliation, including the lateral septum and central amygdala. In addition, voles housed in short day lengths (SD) exhibited higher levels of OTR binding in the central amygdala, and voles exposed to high concentrations of estradiol exhibited less binding in the nucleus accumbens (NAcc) and increased binding in the ventromedial nucleus of the hypothalamus. These results suggest that same-sex social behavior shares common elements with other mammalian social behaviors affected by OT, but that the specific neural pathways through which OT exerts its influence are likely distinct from those known for sexual attachments.

Perinatal influences of melatonin on testicular development and photoperiodic memory in Siberian hamsters.

We assessed the influence of perinatal melatonin on reproductive development and adult responsiveness to melatonin. Testicular growth in an intermediate day length (14 : 10 h light/dark cycle) was substantially reduced in Siberian hamsters gestated by pinealectomised compared to pineal-intact females; gonadal development was normalised in offspring of pinealectomised dams that were pinealectomised at 3-4 days of age. Hamsters deprived of melatonin only during gestation, or both pre- and postnatally, underwent testicular involution during treatment with melatonin in adulthood. Photoperiodic histories acquired prenatally did not endure as long as those acquired by adult hamsters. Hamsters first exposed to melatonin in adulthood were not more proficient in acquiring photoperiodic histories than were normal males. These findings indicate that pre- versus postnatal differences in melatonin signal duration determine rates of testicular development. Exposure to melatonin perinatally does not appear to organise the neuroendocrine substrate that mediates effects of day length and melatonin on the gonads of adult hamsters.

Amelioration of depressed cardiopulmonary reflex control of sympathetic nerve activity by short-term exercise training in male rabbits with heart failure.

The reflex regulation of sympathetic nerve activity has been demonstrated to be impaired in the chronic heart failure (CHF) state compared with the normal condition (Liu JL, Murakami H, and Zucker IH. Circ Res 82: 496-502, 1998). Exercise training (Ex) appears to be beneficial to patients with CHF and has been shown to reduce sympathetic outflow in this disease state (Hambrecht R, Hilbrich L, Erbs S, Gielen S, Fiehn E, Schoene N, and Schuler G. J Am Coll Cardiol 35: 706-713, 2000). We tested the hypothesis that Ex corrects the reduced cardiopulmonary (CP) reflex response to volume expansion in the CHF state. Normal, normal with Ex, CHF, and CHF with Ex (CHF-Ex) groups (n = 10-21) of male New Zealand White rabbits were studied. CHF was induced by chronic ventricular pacing. Rabbits were instrumented to record left ventricular end-diastolic pressure (LVEDP), left ventricular end-diastolic diameter (LVEDD), and renal sympathetic nerve activity (RSNA). Experiments were carried out with the animals in the conscious state. Volume expansion was performed with 6% dextran in normal saline at a rate of 5 ml/min to approximately 20% of estimated plasma volume without any significant effect on mean arterial pressure being exhibited. The relationships between RSNA and LVEDP and between RSNA and LVEDD were determined by linear regression; the slopes served as an index of CP reflex sensitivity. Normal rabbits exhibited a CP reflex sensitivity of -8.4 +/- 1.5%delta RSNA/mmHg. This value fell to 0.0 +/- 1.3%delta RSNA/mmHg in CHF rabbits (P < 0.001). Ex increased CP reflex sensitivity to -5.0 +/- 0.7%delta RSNA/mmHg in CHF-Ex rabbits (P < 0.05 compared with CHF). A similar trend was seen when related to the change in LVEDD. Furthermore, resting RSNA expressed as a percentage of maximum RSNA in response to cigarette smoke was also normalized by Ex in rabbits with CHF. Ex had no effect on these parameters in normal rabbits. These data confirm an impairment of CP reflex sensitivity and sympathoexcitation in CHF vs. normal animals. Ex substantially restored both CP reflex sensitivity and baseline RSNA in CHF animals. Thus Ex beneficially affects reflex regulation in CHF, thereby lowering resting sympathetic nerve activity.

Seasonal control of penile development of Siberian hamsters (Phodopus sungorus) by daylength and testicular hormones.

Seasonal variation in prepubertal penile growth has not previously been studied. The present study assessed the influence of daylength and androgens on penile development in the Siberian hamster (Phodopus sungorus). Adult penile masses were achieved at 18 and 8 weeks of age in hamsters maintained from birth under short (10 h light:14 h dark) versus long (14 h light:10 h dark) daylengths, respectively. Insulin-like growth factor I concentrations, previously implicated in penile growth, did not differ between hamsters maintained in short versus long daylengths. Gonadectomized juvenile males maintained in short and long daylengths and administered testosterone attained adult penile masses well in advance of untreated gonad-intact males maintained in short daylengths. Hamsters from both photoperiods, castrated as juveniles and first treated with testosterone in adulthood, also achieved adult penile masses. The photoinhibited gonad is insufficient to promote penile growth, and prepubertal gonadal secretions during short daylengths are not necessary for eventual penile development. Among young born near the end of the mating season, onset of neuroendocrine refractoriness to short daylengths at about 100 days of age and subsequent gonadal development induces growth in all reproductive tissues. Timing of puberty and increased androgen secretion controlled by daylength are the primary determinants of postnatal penile growth, which may also be affected by prenatal and early postnatal organizational actions of androgens.

Termination of neuroendocrine refractoriness to melatonin in Siberian hamsters (Phodopus sungorus).

Siberian hamsters maintained from birth in a short day length (DL), unlike their long-day counterparts, fail to undergo reproductive development by 5 weeks of age. Instead, reproductive maturation of short-day males is delayed for approximately 20 weeks, at which point neuroendocrine refractoriness to the inhibitory effects of short DLs develops, resulting in growth of the gonads. To terminate refractoriness and re-establish responsiveness to short photoperiods, 10-15 weeks of long-day exposure is required. We assessed whether continuous exposure to long days is necessary to terminate refractoriness or whether the first few weeks of long days initiate a process that culminates several months later in the breaking of refractoriness. Male hamsters refractory to short DLs were transferred to a long-day photoperiod, pinealectomized (PINx) after 0, 3, 6 or 15 weeks, and subsequently infused for 6 weeks with a short-day melatonin signal. This melatonin treatment induces gonadal regression in photosensitive but not in photorefractory hamsters. Six percent of males PINx at week 0 and 88% of those PINx at week 15 underwent gonadal atrophy by the end of the melatonin infusion treatment initiated on week 15. Among hamsters PINx on week 6, 17% versus 76% underwent testicular involution in response to melatonin infusions initiated on week 6 and week 15, respectively. This finding indicates that a fraction of the long days that hamsters experience during spring and summer are sufficient to trigger the processes that restore responsiveness to short DLs. Additional groups of pineal-intact photorefractory animals were given 3, 6 or 15 weeks of long-day exposure and then returned to a short DL for several months; only those treated for 15 weeks terminated refractoriness. The breaking of refractoriness, once triggered by long-day melatonin signals, proceeds to completion only in the absence of short-day melatonin signals.

Itch characteristics in Chinese patients with atopic dermatitis using a new questionnaire for the assessment of pruritus.

BACKGROUND: Although pruritus is the predominant and commonest feature of atopic dermatitis, its clinical characteristics have not been explored. OBJECTIVE: To characterize the clinical pattern and sensory and affective dimensions of the itch experience utilizing a comprehensive itch questionnaire. METHODS: A structured itch questionnaire based on the McGill pain questionnaire was given to 102 Chinese patients with known atopic dermatitis. RESULTS: There were 100 patients with atopic dermatitis who fully filled the questionnaire. In 87% of the patients pruritus appeared on a daily basis. It had a prolonged duration (mean duration 10.7 7.3 years). It involved all body areas mostly in the lower limbs (83%), flexures (76%), upper limbs (71%) and neck (65%). Itch intensity during its peak was nearly twice higher than the itch of a mosquito bite. Itching was most frequent at night (65%), and 84% of patients reported of difficulty falling asleep. Daily life activities which increased the severity of itch were sweat in 96%, dryness in 71%, stress in 71% and physical effort in 73%. The major factors which were found to reduce the intensity of pruritus included: bathing with cold water in 55% and cold ambient environment in 56%. Associated symptoms were heat sensation (51%), sweating (40%) and pain in the pruritic area (45%). The various anti-pruritic therapies had limited long-term effect. The pruritus was bothersome (52%) and a major distress to the patient. The affective score correlated to itch intensity during its peak (r = 0.4, P < 0.001). CONCLUSIONS: The study provided a detailed description of pruritus in atopic dermatitis with new data on affective and sensory dimensions and associated symptoms. The questionnaire was found to be a useful tool in characterization of itch.

Photoperiodic control of oestrous cycles in Syrian hamsters: mediation by the mediobasal hypothalamus.

To assess whether the mediobasal hypothalamus (MBH) is necessary for photoperiodic control of oestrous cycles and prolactin secretion, we tested intact female Syrian hamsters (controls) and those that had sustained unilateral or bilateral lesions of the MBH. All hamsters displayed 4-day oestrous cycles postoperatively in the long-day photoperiod (14 h light/day); control females and those with unilateral MBH damage ceased to undergo oestrous cycles approximately 8 weeks after transfer to a short-day photocycle (10 h light/day), whereas 12 of 15 females with bilateral MBH lesions continued to generate 4-day oestrous cycles throughout 22 weeks in short days. Serum prolactin concentrations were either undetectable or low in all hamsters 8 or 14 weeks after the transfer to short-day lengths, but increased above long-day baseline values by week 22. We conclude that melatonin-binding sites in the MBH mediate suppression of oestrous cycles but not prolactin secretion by short-day lengths; recovery of prolactin secretion in females during prolonged exposure to short-day lengths reflects development of refractoriness to melatonin in a substrate distinct from the MBH. These findings suggest that separate neural pathways mediate photoperiodic control of gonadotropin and prolactin secretion in female hamsters.

Torpor characteristics and energy requirements of furless Siberian hamsters.

After approximately 10 wk of exposure to decreasing day lengths, Siberian hamsters (Phodopus sungorus) begin to display spontaneous torpor bouts several times each week. Torpor is associated with reduced daily energy expenditure and lower food consumption and ameliorates the thermoregulatory challenges of winter. We tested the extent to which the energy savings conferred by daily torpor depend on the presence of an insulative pelage. Female hamsters were housed in a winter day length (8L:16D) at 5 degrees C; daily food intake and torpor characteristics were recorded for 5 wk in shaved (furless) or normal hamsters. Torpor-bout incidence decreased by 62% in furless hamsters, but the duration of individual bouts and the minimum body temperature attained during torpor were unaffected by loss of pelage. Body temperature declined more rapidly during entry into torpor and increased more slowly during arousal from torpor in furless than in control hamsters. Energy savings per torpor bout, assessed by the amount of food consumed on days that included a torpor bout, was substantially greater in normal than in furless hamsters (16.0% vs. 3.3%); this difference likely reflects the increased cost of thermoregulation during torpor, as well as the increased caloric expenditure incurred by furless hamsters during arousal from torpor. An insulative pelage may be a prerequisite for the energetic benefits derived from heterothermy in this species.

A questionnaire for the assessment of pruritus: validation in uremic patients.

A questionnaire was constructed for the evaluation and measurement of pruritus. The questionnaire, based on the short form of the McGill Pain Questionnaire, was tested in 145 patients suffering from uremic pruritus and currently undergoing hemodialysis treatment in 3 centers. The newly developed questionnaire proved to be reliable and provided valid data on the sensory, affective and overall intensity of uremic pruritus. The data suggest that uremic pruritus tends to be prolonged, frequently intense and a major source of distress to the patient. Dialysis was not found to influence the pruritus. The questionnaire may also be useful in pruritus secondary to other causes.

The regulation of sympathetic outflow in heart failure. The roles of angiotensin II, nitric oxide, and exercise training.

Sympatho-excitation is a hallmark of the chronic heart failure (CHF) state. It has long been assumed that this sympatho-excitation is mediated by a reduction in sensory input from cardiopulmonary and arterial baroreceptors. However, recent data suggest that these reflexes may only be important in the initiation of the sympatho-excitatory state and may not be necessary for the sustained increase in sympathetic nerve activity (SNA) in CHF. Two humoral factors that can influence SNA are nitric oxide (NO) and angiotensin II (AngII). Animals with CHF exhibit a downregulation in central gene expression for the neuronal isoform of nitric oxide synthase (nNOS). In addition, blockade of AngII receptors in combination with NO donation reduces SNA in animals with CHF, while NO donation alone has no effect on SNA. Chronic exercise training (EX) reduces both plasma AngII and SNA in rabbits with CHF while improving baroreflex function. Blockade of AT1 receptors enhances baroreflex function in non-EX CHF rabbits, but has little effect in EX CHF rabbits. These data suggest that the sympatho-excitatory state that is typical of CHF is, in part, due to changes in AngII and NO. Depressed baroreflex function and the elevated SNA can be improved by EX in animals with CHF.

Energy intake and fur in summer- and winter-acclimated Siberian hamsters (Phodopus sungorus).

Few studies have directly addressed the impact of fur on seasonal changes in energy intake. The daily food intake of Siberian hamsters (Phodopus sungorus) was measured under simulated summer and winter conditions in intact animals and those with varying amounts of pelage removed. Energy intake increased up to 44% above baseline control values for approximately 2-3 wk after complete shaving. Increases in food intake varied with condition and were greater in hamsters housed in short than long day lengths and at low (5 degrees C) than moderate (23 degrees C) ambient temperatures. Removal of 8 cm(2) of dorsal fur, equivalent to 30% of the total dorsal fur surface, increased food intake, but removal of 4 cm(2) had no effect. An 8-cm(2) fur extirpation from the ventral surface did not increase food consumption. Food intake was not influenced differentially by fur removal from above brown adipose tissue hot spots. Fur plays a greater role in energy balance in winter- than summer-acclimated hamsters and conserves energy under a wide range of environmental conditions.

Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure.

Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320--340 beats/min for 3--4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754,142 (a combined ET(A) and ET(B) receptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg. kg(-1) x h(-1) for 48 h). In addition, five rabbits with CHF were treated with the specific ET(A) receptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 +/- 4.9 vs. 27.0 +/- 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 +/- 0.19 vs. 6.04 +/- 0.73, P < 0.001). L-754,142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.

Refractoriness to melatonin occurs independently at multiple brain sites in Siberian hamsters.

The mid-winter development of refractoriness to melatonin (Mel) triggers recrudescence of the atrophied reproductive apparatus of rodents. As a consequence, over-wintering animals become reproductively competent just before the onset of spring conditions favorable for breeding. The neural target tissues that cease to respond to winter Mel signals have not been identified. We now report that the suprachiasmatic nucleus of the hypothalamus, which contains the principal circadian clock, and the reuniens and paraventricular nuclei of the thalamus, each independently becomes refractory to melatonin. Small implants of Mel that were left in place for 40 wk and that act locally on these brain nuclei, induced testicular regression within 6 wk in male Siberian hamsters; 12 wk later Mel implants no longer suppressed reproduction and gonadal recrudescence ensued. Hamsters that were then given a systemic Mel infusion s.c. immediately initiated a second gonadal regression, implying that neurons at each site become refractory to Mel without compromising responsiveness of other Mel target tissues. Refractoriness occurs locally and independently at each neural target tissue, rather than in a separate "refractoriness" substrate. Restricted, target-specific actions of Mel are consistent with the independent regulation by day length of the several behavioral and physiological traits that vary seasonally in mammals.

Low ambient temperature accelerates short-day responses in Siberian hamsters by altering responsiveness to melatonin.

Exposure to low ambient temperatures (Ta) accelerates appearance of the winter phenotype in Siberian hamsters transferred from long to short day lengths. Because melatonin transduces the effects of day length on the neuroendocrine axis, the authors assessed whether low Ta promotes the transition to winterlike traits by accelerating the onset of increased nocturnal melatonin secretion or by enhancing responsiveness to melatonin in short day lengths. Male hamsters were transferred from 16L (16 h light/day) to 8L (8 h light/day) photoperiods and held at 5 degrees C or 22 degrees C. Locomotor activity was recorded continuously, and body mass, testis size, and pelage color were determined biweekly for 8 weeks. The duration of nocturnal locomotion (alpha), a reliable indicator of the duration of nocturnal melatonin secretion, lengthened significantly earlier in hamsters exposed to a Ta of 5 degrees C than 22 degrees C. Cold exposure increased the proportion of hamsters that were photoresponsive: gonadal regression in short days increased from 44% at 22 degrees C to 81% at 5 degrees C (p < 0.05); low Ta did not, however, accelerate testicular regression in animals that were photoresponsive. Nonphotoresponsive animals at 5 degrees C temporarily had longer alphas during the first 4 weeks in short days and significant decreases in body mass and testicular size that were reversed during the ensuing weeks when alpha decreased. In a 2nd experiment, pinealectomized male hamsters infused for 10 h/day with melatonin for 2 weeks had significantly lower body and testes masses when maintained at 5 degrees C but not 22 degrees C. Low-ambient temperature appears to accelerate the appearance of the winter phenotype primarily by increasing target tissue responsiveness to melatonin and to a lesser extent by augmenting the rate at which the duration of nocturnal melatonin secretion increases in short day lengths.

Chronic exercise reduces sympathetic nerve activity in rabbits with pacing-induced heart failure: A role for angiotensin II.

BACKGROUND: Chronic exercise (EX) improves the quality of life and increases the survival of patients with chronic heart failure (CHF). Because sympathetic nerve activity is elevated in the CHF state, it is possible that EX is beneficial in this disease due to a decrease in sympathetic outflow. METHODS AND RESULTS: We evaluated arterial baroreflex function and resting renal sympathetic nerve activity (RSNA) in EX normal and CHF rabbits before and after angiotensin II type 1 (AT(1)) receptor blockade. Four groups of rabbits were studied: a normal non-EX group, a normal EX group, a CHF non-EX group, and a CHF EX group. EX lowered resting RSNA in rabbits with CHF but not in normal rabbits. In addition, EX increased arterial baroreflex sensitivity in the CHF group (heart rate slope: CHF 1. 7+/-0.3 bpm/mm Hg, EX CHF 4.9+/-0.3 bpm/mm Hg; P:<0.01; RSNA slope: CHF 2.2+/-0.2%max/mm Hg, EX CHF 5.7+/-0.4%max/mm Hg; P:<0.01. AT(1) receptor blockade enhanced baroreflex sensitivity in the non-EX CHF rabbits but had no effect in EX CHF rabbits. Concomitant with this effect, EX lowered the elevated plasma angiotensin II concentration in the CHF group. A significant positive correlation was observed between sympathetic nerve activity and plasma angiotensin II. CONCLUSIONS: These data strongly suggest that EX reduces the sympathoexcitatory state in the setting of CHF. Enhanced arterial baroreflex sensitivity may contribute to this reduction. In addition, EX lowers plasma angiotensin II concentration in CHF. These data further suggest that the lowering of angiotensin II may contribute to the decrease in sympathetic nerve activity after EX in the CHF state.

Testicular development in Siberian hamsters depends on frequency and pattern of melatonin signals.

We investigated the impact of frequency and pattern of melatonin signals on reproductive development in Siberian hamsters. Juvenile males gestated in short day lengths and housed in constant illumination to suppress melatonin secretion were infused with melatonin for 5 h either once or twice per day for 20 days. Melatonin infusions at either frequency produced equivalent increases in testes and body weights that exceeded those of animals infused with saline but were indistinguishable from those of hamsters transferred to long day lengths. The reproductive system appears to be maximally stimulated by a single short melatonin signal each day. Other animals kept from birth in a short photoperiod were treated 6 h after onset of darkness with the beta-adrenergic receptor antagonist DL-propranolol to shorten melatonin secretion on the night of injection but not on subsequent nights. This permitted interpolation of short nightly melatonin signals of 4-5 h duration against a background of long melatonin signals of 10-12 h duration on other nights. Treatment regimes that maintained a 1:1 ratio of short to long melatonin signals for 8 wk stimulated reproductive development; a 1:2 signal ratio, in each of three different patterns, was uniformly ineffective. The number of successive short melatonin signals had little influence on the interval across which successive melatonin signals were summated to influence photoperiodic traits. The neuroendocrine axis appears more responsive to short melatonin signal frequency than pattern for development of the summer phenotype.