Stress triggers different pathophysiological mechanisms in younger and older cardiomyopathic hamsters.

OBJECTIVES: Because cardiomyopathic hamsters (CMHs) in the lesion-forming period of their disease are more susceptible to the lethal effects of stress than older CMHs, we tested the hypothesis that different pathophysiological effects of stress may occur: coronary vasospasm in younger CMHs and congestive heart failure in older ones. METHODS: CMHs aged 2.5 and 6.5 months were stressed with 2 h supine cold immobilization for 5 consecutive days. Three, 5 and 7 days after stress, the hearts were excised and perfused using a modified Langendorff system. Maximum +/- dP/dt, developed pressure, ventricular relaxation time (Tau) and coronary vascular resistance (CVR) were recorded and CVR was also measured following coronary infusion of arginine vasopressin (AVP). RESULTS: Stress produced ventricular dysfunction (decreased maximum +/- dP/dt, developed pressure, and increased Tau) in older CMHs (P < 0.05) but not in younger CMHs. Baseline CVR in younger CMHs was significantly higher than in older CMHs (P < 0.01) and AVP infusion produced a bigger increase in CVR in younger stressed CMHs than in either younger nonstressed or older stressed CMHs (P < 0.05). CONCLUSION: The younger CMH heart exhibits greater resting vascular tone and stress produces coronary vasoconstriction that is consistent with coronary spasm. In contrast, the older CMH experiences a decrease in cardiac function which remains 7 days after stress and indicates an exacerbation of CHF from the mild form existing prior to stress. The lethal effects of stress may occur because of the activation of different pathological processes in younger and older CMHs.

Thyrotropin-like immunoreactivity in the pituitary and three brain regions of the female rat: diurnal variations and the effect of thyroidectomy.

A method for extracting and assaying TSH-like immunoreactivity (TSH-LI) in regions of the central nervous systems (CNS) of individual rats was developed and validated. Serial dilutions of tissue extracts paralleled dilutions of purified rat TSH standard in the RIA, and tissue TSH-LI comigrated electrophoretically with TSH standard. TSH-LI was measured in the pituitary (PIT), the medial basal hypothalamus (MBH), the remainder of the hypothalamus (HYPO), and the cerebral cortex (CC). Female rats were maintained on a normal 12-h light, 12-h dark cycle (LD; onset of light, 0730 h) or an inverted 12-h light, 12-h dark cycle (DL; onset of light, 1930 h) for 3 weeks and then killed at 4-h intervals throughout the day. Another group of rats on the LD photoperiod were either thyroidectomized or sham thyroidectomized and killed 3 weeks later at 1000 h. Diurnal variations of TSH-LI were present in the PIT, MBH, HYPO, and CC on the LD photoperiod (P less than 0.05). The acrophases of MBH, HYPO, and CC TSH-LI diurnal variations occurred soon after the onset of darkness, whereas the PIT TSH-LI variation peaked soon after the onset of light. Inverting the photoperiod inverted the PIT TSH-LI diurnal variation, but central nervous system TSH-LI variations were not phase shifted after 3 weeks on the inverted photoperiod. Thyroidectomy elevated plasma and MBH TSH-LI levels (P less than 0.05), but PIT, HYPO, and CC TSH-LI levels were not significantly different from those in sham-operated controls. These results indicated that brain TSH concentrations could change under different physiological states independently of changes in PIT or plasma TSH. Although brain TSH exhibited diurnal variations, the data suggested that the phase of these variations was not set by the light-dark cycle.

Diurnal variations of plasma thyrotropin, thyroxine, and triiodothyronine in female rats are phase shifted after inversion of the photoperiod.

The present study examined plasma TSH, T4, and T3 concentrations in rats throughout the day to determine if diurnal variations of these hormones occurred. Female rats on a 12-h light, 12-h dark cycle (onset of light, 0730 h) were sampled by cardiac puncture at 2-h intervals throughout the day on 2 days, 1 week apart. Significant diurnal variations of plasma TSH, T4, and T3 were detected (P less than 0.01), Peak TSH concentrations occurred soon after the onset of light, whereas T4 and T3 concentrations peaked 3-4 h later. After these variations were detected, the effect of inverting the photoperiod was examined. Female rats were placed on 12-h light,, 12-h dark cycles, with the onset of light at 0730 h (LD) or 1930 h (DL). After 3 weeks, rats from each group were killed by decapitation at 4-h intervals throughout the day, and trunk blood was collected. Diurnal variations in plasma TSH, T4, and T3 (P less than 0.01) were similar to those found with 2-h sampling intervals in the previous experiment, and plasma corticosterone and PRL rhythms peaked near the onset of darkness (P less than 0.05). Inversion of the photoperiod phase shifted all diurnal variations, such that they maintained a similar phase relationship to the light-dark cycle on both LD and DL photoperiods. These results indicated that diurnal variations of plasma TSH, T4, and T3 concentrations could be repeatedly detected with different sampling protocols. These variations were phase shifted by inverting the photoperiod, which indicated that some aspect of the light-dark cycle can act to set the phase of these diurnal variations in the pituitary-thyroid axis.

Adrenal innervation may be an extrapituitary mechanism able to regulate adrenocortical rhythmicity in rats.

The daily rhythm of plasma corticosteroid concentration was studied in nonhypophysectomized rats and in hypophysectomized rats implanted with beeswax pellets containing ACTH and T4. In the first experiment, male hypophysectomized rats were placed on a 12-h light, 12-h dark cycle (onset of light, 0600 h) with food and water available ad libitum. Beeswax pellets containing 1.5 mg ACTH and 150 micrograms T4 were implanted sc in these rats. Beginning 4 days after the implantation of ACTH and T4, daily rhythms of plasma corticosteroid concentration were detected in these rats on 3 successive days. The injection of sodium pentobarbital (40 mg/kg BW) or atropine sulfate (10 mg/kg BW) ip at 1200 h blocked the expected rise in plasma corticosteroid concentration at 1800 h in both these rats and a group of intact rats. In the second experiment, adrenal innervation was disrupted by spinal cord transection at the T-7 level. L-1-transected rats served as operated controls, and a third group was maintained as unoperated controls. One week after surgery, daily rhythms of plasma corticosteroid concentration were present in both unoperated and L-1 controls (P less than 0.01) but not in the T-7-transected rats. Inasmuch as an extrapituitary mechanism was capable of maintaining adrenocortical rhythmicity in hypophysectomized rats and disruption of adrenal innervation suppressed adrenocortical rhythmicity, it was hypothesized that adrenal innervation may be an extrapituitary mechanism which has a role in adrenocortical rhythmicity.

Extrapituitary regulation of the circadian rhythm of plasma corticosteroid concentration in rats.

Intravascular injections of adrenocorticotropic hormone in hypophysectomized rats were approximately 3 times more effective in stimulating increases in plasma corticosteroid concentration when given at the offset rather than the onset of the daily photoperiod (12 h:12 h light-dark cycle). Reversal of the photoperiodic schedule produced a reversal in the corticosteroid response after 5 days. Similar temporal variations in androgen and T4 responses to LH and TSH were not obtained. Although plasma corticosteroid concentrations were maintained at normal intermediate levels in rats with adrenal autotransplants, daily variations were not demonstrable. These results indicate that the circadian rhythm of plasma corticosteroid concentration is regulated by way of neural pathways to the adrenal.

Interactions among the effects of aging, chronic disease, and stress on adrenocortical function in Syrian hamsters.

This study examined the effects of aging and chronic congestive heart failure on plasma corticosterone and cortisol levels in hamsters. It also assessed the effects of aging and heart failure on glucocorticoid responses to acute and chronic stress. Aging in healthy hamsters increased plasma cortisol levels, decreased corticosterone levels, and did not change total glucocorticoid levels. A similar pattern occurred as cardiomyopathic (CM) hamsters aged, until they developed severe heart failure. Plasma cortisol levels fell in CM hamsters with severe heart failure, and corticosterone levels remained low, so total glucocorticoid levels fell. Adrenocortical function similarly declined in very old healthy hamsters near the ends of their lives. Adrenocortical responses to acute and chronic stress were diminished in old healthy hamsters, and heart failure in CM hamsters also reduced the glucocorticoid responses to chronic stress. However, heart failure greatly enhanced the cortisol and total glucocorticoid responses to acute stress, but not that of corticosterone. These data suggest a number of conclusions. First, aging clearly changes the the ratio of corticosterone to cortisol in hamster plasma without changing total glucocorticoid levels and blunts adrenocortical responses to acute and chronic stress. Second, ill health, in the form of severe heart failure in CM hamsters and very old age in health hamsters, decreases adrenocortical function. At the same time, heart failure greatly enhances cortisol responses to acute stress. These results indicate that aging and chronic disease in hamsters have many similar effects on adrenocortical function, but that disease alone sensitizes them to the effects of acute stress.

The detrimental effects of spinal cord injury on spermatogenesis in the rat is partially reversed by testosterone, but enhanced by follicle-stimulating hormone.

Our previous studies have demonstrated that impaired spermatogenesis during the acute phase of spinal cord injury (SCI) is preceded by a transient (but significant) suppression of serum FSH, LH, and testosterone (T) concentrations. It is hypothesized that hormonal deprivation may impair Sertoli cell function, leading to the loss of spermatogonia, degeneration of spermatogenic cells, and eventual regression of the seminiferous epithelium. The current study examined the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and Sertoli cell functions in SCI rats. Implantation of T capsules (TC, 2 x 5 cm) attenuated some of the spermatogenic lesions and maintained qualitatively complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast, daily injections of 0.1 U of FSH alone, or in combination with TC implants, paradoxically enhanced the regression of spermatogenesis in SCI rats. At this time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes in SCI rats have decreased by 25-30%. Though not prevented by TC implants, the decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further enhanced when FSH-treated rats also received TC implants. The intratesticular T concentration in untreated and FSH-treated SCI rats was not different from that of sham control rats, but it decreased by more than 95% in those SCI rats given TC implants alone. These results demonstrate that impairment of spermatogenesis during the acute phase of SCI is not related to the availability of FSH and/or T. Northern blot analysis revealed an increase in androgen receptor messenger RNA (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but persisted when FSH was also given. In contrast, the levels of FSH-receptor, androgen binding protein, and transferrin mRNA were not affected by SCI but were significantly higher in those SCI rats given FSH alone or in combination with TC. TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats, without concomitant change in those for FSH-receptor and ABP. The changes in Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal events elicited by these hormones, thus contributing to abnormal epithelial environments and regression of spermatogenesis. Maintenance of spermatogenesis in SCI rats by exogenous T suggests the feasibility of using exogenous hormones to impede the detrimental effects of SCI on spermatogenesis. This approach may have clinical applicability for the preservation of spermatogenic functions in SCI men.

Delayed startle sensitization distinguishes rats exposed to one or three stress sessions: further evidence toward an animal model of PTSD.

Posttraumatic stress disorder (PTSD) may occur in humans exposed chronically to stressors or after a single exposure to a traumatic event. A distinguishing feature of patients with PTSD is an exaggerated startle response, evident long after the traumatic event. We have observed similar abnormalities in our animal model of a chronic stress state. Rats exposed to 3 days (3DS) of our stress regimen (2-hr sessions of 40, 2 mA tailshocks) have exhibited a consistent pattern of persistent physiological and behavioral abnormalities including an exaggerated startle response several days after stressor cessation. In contrast, rats exposed to a single stress session (1DS) have exhibited many, but not all, of the persistent abnormalities displayed by 3DS rats. The present experiment compared the startle responding of 3DS and 1DS rats 4, 7, and 10 days after stressor cessation. Consistent with previous work, stressed rats exhibited elevated basal plasma corticosterone (CORT) levels the first day poststressor. These CORT levels were sensitive to the number of stressor exposures with higher CORT levels in 3DS rats than in 1DS rats. As for startle responding, the 1DS rats exhibited an exaggerated startle response 7 days poststressor, whereas startle sensitization was apparent 10 days poststressor in 3DS rats. Thus, the appearance of an exaggerated startle response after stressor cessation appears to be related to the number of stress session exposures. These animal models, the 3DS and 1DS rats, may be useful to gain insight into the neurobehavioral changes associated with PTSD.

Adrenocortical and behavioral responses to repeated stressors: toward an animal model of chronic stress and stress-related mental illness.

Research in chronic stress has been hampered by the absence of an operational definition for that condition. To explore possible criteria for chronic stress, we repeatedly exposed rats to 2 hr of tail shock per day. After several days, we found elevated prestress corticosterone levels and abnormal behavior, including decreased food consumption, fear-like suppression of activity immediately before stress, greater hesitancy to drop from a suspended wire, and decreased exploratory behavior in a novel environment. A less intensely stressed group of rats also had elevated prestress corticosterone levels, but not the abnormal behaviors that persisted in shocked rats after the stress sessions were discontinued. We propose that abnormalities in both adrenocortical function and behavior are a better marker for chronic stress than abnormalities in either of these systems alone. The animal model we have described may be useful for studying factors that contribute to development of chronic stress or PTSD.

Effect of stress and food restriction on blood pressure and lifespan of Dahl salt-sensitive rats.

OBJECTIVE: To evaluate the long-term consequences of stress in rats with genetic hypertension. DESIGN: Rapp-Dahl salt-sensitive rats, maintained on a low-salt diet, were stressed periodically over 8 weeks during which time their blood pressures were measured. In experiment 1 both stressed and unstressed control rats were given ad libitum access to food. Because of significant differences in body weights, in experiment 2 the unstressed controls were pair-fed to maintain their food intake at a level similar to that of the stressed rats. METHODS: Rats were subjected to 2-h sessions of supine immobilization stress 5 days a week every other week for 8 weeks. Blood pressures were measured during non-stress weeks, at least 4 days after the last exposure to the stressor and at monthly intervals thereafter. Survival curves were also established. RESULTS: In experiment 1 stressed rats developed hypertension at a slower rate than controls and lived significantly longer, but also weighted significantly less than controls, presumably because of diminished food intake. In experiment 2, in which food intake was controlled, body weights were similar in the two groups of rats, and hypertension developed at the same rate in both groups. Survival curves were not significantly different. Food restriction extended life compared with free feeding. CONCLUSIONS: Stress need not have long-term, deleterious health consequences in rats with genetically inherited hypertension, whereas caloric restriction is protective.

Comparison of dobutamine and exercise echocardiography for detecting coronary artery disease.

There has been no study comparing the efficacy of dobutamine and exercise echocardiography in detecting coronary artery disease (CAD) or their physiologic effects at ischemic threshold in the same group of patients. To accomplish this, 52 patients presenting for coronary angiography underwent supine ergometer exercise and dobutamine echocardiography. Compared with angiography, the overall sensitivity of detecting CAD was 78% for exercise and 86% for dobutamine echocardiography (p = NS). The sensitivities of detecting patients with 1-, 2-, 3- and multivessel CAD with exercise echocardiography were 63, 80, 100 and 90%, respectively, and with dobutamine echocardiography 75, 90, 100 and 95%, respectively (p = NS, exercise vs dobutamine). The specificity of both tests was 87%. At ischemic threshold, heart rate was significantly lower with dobutamine than with exercise echocardiography (91 +/- 3 vs 114 +/- 3 beats/min; p < 0.001), systolic blood pressure was significantly lower with dobutamine testing (155 +/- 5 vs 176 +/- 6 mm Hg; p < 0.01), and rate-pressure product was significantly lower with dobutamine stress (14.1 +/- 0.7 vs 19.8 +/- 0.8 x 10(3) beats/min x mm Hg; p < 0.001). It is concluded that the efficacy of detecting CAD by exercise and dobutamine echocardiography is comparable, and the physiology at ischemic threshold of the 2 methods is significantly different and suggests a different means of inducing myocardial ischemia.

Use of motor performance tests to differentiate aging effects from disease effects.

The present study has demonstrated that behavioral testing can provide non-invasive methods for monitoring the time-courses of aging and disease processes. Performance on two of our tests changed linearly with increasing age in both cardiomyopathic and healthy hamsters, but these changes occurred at an earlier age in the CM hamsters than in healthy control hamsters. In addition, healthy hamsters showed age-related changes in performance on some tests, while sick CM hamsters did not show parallel changes. These results indicate that disease can modify the rate of change in some markers of aging, and thus they suggest that disease might be able to modify the aging process. However, such a preliminary hypothesis requires much further work. Performance on another behavioral test was shown to be stable throughout much of the lifespan of healthy hamsters, and yet disease in CM hamsters was clearly able to affect it. Thus it was possible to find some tests which discriminated between aging and disease effects, but only because the time-course of the disease we were studying was well defined. Most importantly, these results have suggested a way of thinking about the problem of disease in aging studies that may be more fruitful than others previously used. Examining the changes over time in both healthy subjects (putatively disease-free) and those with disease should allow one to determine which age-related changes are dependent on the presence of organic disease and to separate these from the changes which might inevitably occur solely from increasing age.

Effect of stressor intensity on habituation and sensitization of glucocorticoid responses in rats.

This experiment was designed to study the effect of stressor intensity on habituation/sensitization of the adrenocortical stress response in rats. Rats were given 18 shocks in 3-hr daily sessions for 8 days, and a single shock probe before the sessions was used to determine how adrenocortical responsiveness changed with repeated exposure to the stress sessions. When lower intensity shock was given, the changes in plasma corticosterone response to shock probes followed a U-shaped curve--with a response that first habituated to no-shock control levels but later returned to the same magnitude as seen on the 1st probe day. Plasma corticosterone responses in rats given higher intensity shock never habituated and instead demonstrated an increased response indicative of sensitization; a temporal delay of 1 week occurred before sensitization developed. Responsiveness to exogenous adrenocorticotropin 24 hr after the last stress session was monotonically related to the intensity of the stressor presented during the experimental sessions. These data are consistent with the rule from the habituation literature that stimulus intensity is inversely related to the magnitude of habituation. Thus the data extend the dual process theory of Groves and Thompson (1970) to an endocrine respondent. The data also suggest that an explanation as to discrepancies in the literature concerning adrenocortical response to repeated presentation of stressors may relate to differences in the stressor parameters used.

Effects of exposure to stressors of varying predictability on adrenal function in rats.

For 5 days, rats were exposed to shocks that were signalled by a light 0, 33, 66, or 100% of the time. Basal hormone levels and responses to a light-shock pair were measured daily. Greater predictability was associated with higher basal plasma corticosterone and norepinephrine levels indicative of chronic stress. Habituation of the corticosterone response was also less in the groups with greater predictability. However, predictability did not affect plasma prolactin or epinephrine responses. Because the endocrine systems responded differently, it is unlikely that the changes were due to a unitary process. Greater predictability appeared to be more stressful in this paradigm. Both associative and nonassociative factors have major roles in determining the hormonal responses to repeated presentation of stressors.

Effects of chronic alprazolam treatment on plasma concentrations of glucocorticoids, thyroid hormones, and testosterone in cardiomyopathic hamsters.

In the first of two experiments, young male cardiomyopathic hamsters were injected intraperitoneally twice a day for 29 days with 8 mg alprazolam/kg body weight or saline. Three hours after the same injections on day 30, they were sacrificed and plasma hormone levels were measured. Alprazolam increased cortisol, total glucocorticoid and triiodothyronine levels. It did not affect corticosterone, thyroxine or testosterone levels. The same protocol was used in a second experiment, except the controls received vehicle and a third group was treated with 48 mg diazepam/kg body weight. Alprazolam again increased cortisol and total glucocorticoid levels, but not those of corticosterone. On the other hand, diazepam increased both cortisol and corticosterone levels. These experiments suggest that chronic benzodiazepine treatment can affect adrenocortical function and perhaps some aspects of thyroid function.

The relationship between circadian rhythmicity and vasoactive intestinal polypeptide in the suprachiasmatic nucleus of congenitally anophthalmic mice.

To date, the search for the clock component that is both necessary and sufficient for generation of circadian rhythms has relied primarily on experimental interventions such as lesions and transplantation of fetal SCN. While these approaches have been fruitful, lesions disrupt adjacent host tissue and fiber pathways, and donor tissue is likewise subject to trauma during harvest and transplantation. The current investigation has used congenitally anophthalmic (eyeless) mice to ask whether VIP-IR SCN neurons are necessary and sufficient for generation of circadian rhythms. In this animal model, arrhythmic mice occur naturally, together with their rhythmic littermates. We have combined recording of wheel-running activity with light microscopic immunocytochemistry for vasoactive intestinal polypeptide (VIP) and cytoarchitectural analysis of the suprachiasmatic nuclei (SCN) in rhythmic and arrhythmic anophthalmic mice. Our data provide the first definitive evidence that the presence of VIP neurons in the SCN is not sufficient for generation of circadian locomotor rhythms.

Diurnal variations in vasoactive intestinal polypeptide-like immunoreactivity in the suprachiasmatic nucleus of congenitally anophthalmic mice.

The present study has combined recording of circadian locomotor rhythms with light microscopic immunocytochemistry for vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus (SCN) of congenitally anophthalmic mice. These mice, which never develop retinae or optic nerves and do not perceive light, are thus in constant darkness. Our data show a circadian rhythm in expression of VIP in the SCN of anophthalmic mice--expression is maximal during late subjective night/early subjective day and minimal in late subjective day/early subjective night. These observations support the hypothesis that expression of VIP is related to regulation of circadian rhythms by the SCN.

Suppression and recovery of spermatogenesis following spinal cord injury in the rat.

Recently, we reported that changes in spermatogenesis in adult rats during acute phase (within 2 weeks) of spinal cord injury (SCI) were associated with a suppression of pituitary-testis hormone axis, and these effects mimic those that occur after hormone deprivation. In this study, we examined the long-term (>4 weeks) effects of SCI on spermatogenesis and its recovery. Results of this study reveal that while serum follicle stimulating hormone, luteinizing hormone, and testosterone levels in SCI rats recovered within 1 month after the injury, their spermatogenesis continued to regress. By 3 months, spermatogenesis in 70% of SCI rats has totally regressed, characterized by the absence of proliferating spermatogonia; these effects could not be prevented by an otherwise effective regimen of testosterone treatment. Sertoli cells in the regressed seminiferous tubules exhibited unusual behavior, characterized by the formation of multiple cell layers and/or aggregates that extended into the tubular lumen. Active spermatogenesis was observed in nine of the 19 SCI rats by 6 months, seven of which had complete spermatogenesis, but with persisting abnormalities. These results demonstrate that SCI results in total, but reversible, regression of spermatogenesis. Failure to prevent such effects by an otherwise effective exogenous testosterone regimen suggests that non-endocrine factors are involved in the SCI effects on spermatogenesis. The unusual Sertoli cell localization in the regressed testes may have been triggered by the loss of proliferating spermatogonia and may be involved in subsequent spermatogenic recovery.

The effects of spinal cord injury on the status of messenger ribonucleic acid for TRPM 2 and androgen receptor in the prostate of the rat.

The prostate is one of the male accessory sex glands that produce fluid components of the seminal plasma. In addition to androgen, a normal innervation of the prostate is believed to be important for maintaining normal function of the prostate. Previously we noted that, in the rat, the weight of the prostate decreased following surgically induced spinal cord injury (SCI). This observation suggests that growth, and possibly function, of the prostate may be compromised after SCI. To explore this possibility, we examined the effects of SCI on the androgen-related biochemical properties and morphology of the prostate in the rat at various times after surgically induced SCI. SCI resulted in an acute decrease in prostate weight and an increase in steady state level of mRNA for testosterone-repressed prostate message 2 (TRPM 2) during the first 2 weeks postinjury. These changes perhaps relate to an increase in cell death or a decrease in secretory activity due to an acute suppression of serum testosterone after the injury. Concomitantly, there was a transient, but significant, decrease in the steady state level of androgen receptor (AR) mRNA in the prostate during the first 2 weeks after SCI, an indication of an altered autoregulation of AR by its own ligand. Despite the fact that growth of the prostate, as indicated by weight increase, in SCI rats resumed 2 weeks postinjury, prostate weights were persistently lower in SCI rats than sham-operated controls for at least 3 months. Furthermore, prostate TRPM 2 mRNA levels remained elevated throughout the recovery period even after a normal prostate weight had been restored. In addition, a decrease in the height of ventral prostate epithelial cells was noted in SCI rats 28 and 90 days postinjury. These results demonstrate a prolonged effect of SCI on prostate function. These findings and our unreported observation of persistently smaller seminal vesicles in the same groups of SCI rats suggest that functions of male accessory sex glands may also be compromised after SCI. These changes may affect biochemical properties of the secretory products of these glands and may provide some explanation for the reported changes in the composition of the seminal plasma and abnormal sperm motility seen in the semen of SCI men.

Acute effects of spinal cord injury on the pituitary-testicular hormone axis and Sertoli cell functions: a time course study.

The present study investigated the time course of the onset of the abnormalities in spermatogenesis following spinal cord injury, and their relationship to changes in the pituitary testicular hormonal axis and Sertoli cell function. Spinal cord injury (SCI) was induced in adult male rats by surgical transection of the spinal cord at the level of T9 and L1 vertebrae. Animals were killed 3, 7, and 14 days after the operation. As early as 3 days following SCI, abnormalities in spermatogenesis, including delayed spermiation and vacuolization of the nucleus of spermatids, were noted in both the T9 and L1 animals. By 14 days, other lesions, including phagocytosis of mature spermatids, incomplete cellular associations, and total regression of seminiferous epithelium, became apparent. Concurrently a transient but significant (P < 0.05) suppression of serum follicle-stimulating hormone (FSH) occurred in the T9 animals, and a suppression of serum luteinizing hormone (LH) occurred in both the T9 and the L1 animals 3 days after the surgery. This was accompanied by a suppression of testicular and serum testosterone levels (P < 0.05, P < 0.01, respectively). Most of the hormonal parameters had recovered and were not different from those of sham-operated animals by 14 days (P > 0.10). Northern blot analysis of testicular poly(A)+ RNA revealed a transient but significant reduction in the steady-state level of the 2.7-kilobase (kb) Sertoli cell transferrin mRNA transcript in both the T9 and the L1 animals 3 days after the operation (P < 0.05). On the other hand, the 1.7-kb androgen binding protein (ABP) mRNA remained unaffected during the 2-week study period. The steady-state level of mRNA transcripts for spermatogenic cell-specific hemiferrin and spermatid specific transition protein 2 and protamine 1 also remained unchanged. These results suggest that spinal cord injury will result in a temporary, but profound, effect on the pituitary-testicular hormone axis. These changes may impair certain aspects of Sertoli cell function that could render these cells incapable of supporting normal spermatogenesis. However, the severity of spermatogenic lesions and the disparate responses of the two major Sertoli cell proteins make it unlikely that hormone deficiency is the only mechanism responsible for the impaired spermatogenesis following spinal cord injury.