Search PubMedSearch

Biomedical subjects

C L Sisk

Publications and source records attributed to C L Sisk.

17 recordsLinked to original sources

Photoperiodic regulation of prolactin release in male hamsters with hypothalamic knife cuts.

Horizontal knife cuts placed dorsal to the paraventricular nucleus (PVN) of the hypothalamus prevent testicular regression in hamsters kept in short days. We examined the effects of these cuts on the photoperiodic modulation of the postcastration rise in gonadotropins, as well as on the release of prolactin in castrated and gonadally intact animals. The cuts blocked the inhibitory effects of short daylengths on the postcastration rise in circulating levels of gonadotropins. However, the cuts did not prevent the reduction in prolactin levels induced by short daylengths in castrated and gonadally intact animals. We conclude that dorsal connections of the PVN are not required for transduction of photoperiodic information used to regulate prolactin release. The knife cuts may remove tonic inhibitory influences on the release of follicle-stimulating hormone and luteinizing hormone, and thus produce elevated gonadotropin levels that mask the effects of nonstimulatory photoperiods on testicular size.

Animals

Photoperiod modulates pubertal shifts in behavioral responsiveness to testosterone.

This study examined the effect of photoperiod on pubertal maturation of steroid-dependent reproductive behaviors in male European ferrets (Mustela putorius furo). In the first experiment, levels of neck gripping, mounting, and pelvic thrusting in gonadally intact prepubertal (PRE) ferrets were compared with those of adults that had undergone puberty either while housed in short days (8 hr light/16 hr darkness per day; SD), or after transfer from SD to long days (18 hr light/6 hr darkness per day; LD) at 12 weeks of age. Both LD and SD adults demonstrated significantly greater amounts of neck gripping and mounting than PRE males. In addition, a significantly greater proportion of adults in both SD and LD displayed at least one incidence of the three behaviors compared to PRE ferrets. There were no statistically significant differences in behavior of the gonadally intact LD and SD adults. In the second experiment, dose-response curves for behavioral responses to subcutaneous injections of 0, 0.5, 1.25, 2.5, 5, and 10 mg/kg testosterone propionate (TP) in oil were generated in castrated PRE, SD, and LD males. The lowest dose of TP elicited significantly greater amounts of all three behaviors in LD adults than in PRE ferrets. In addition, levels of mounting and thrusting elicited by the lowest dose of TP were significantly greater in LD adults than in SD adults. These data indicate that pubertal activation of male sexual behavior in male ferrets is accompanied by a pubertal increase in responsiveness to the behavioral effects of testosterone. Furthermore, the degree of behavioral responsiveness of adult ferrets to testosterone is modulated by environmental photoperiod experienced during reproductive maturation.

Animals

Testosterone in MPOA elicits behavioral but not neuroendocrine responses in ferrets.

The amount of time male ferrets were engaged in neck gripping, mounting, and thrusting was quantified in 30-min tests with a receptive female before and after castration. Bilateral cannulae containing a total of approximately 2 mg testosterone propionate (TP) in cocoa butter were then stereotaxically aimed at the medial preoptic area (MPOA). Tests for sexual behavior were conducted on days 3, 7, 14, and 21 postimplantation. Ferrets were histologically categorized as either 1) Miss (implants not in MPOA), 2) Unilateral implant in MPOA, or 3) Bilateral implants in MPOA. The mean amount of time spent neck gripping, mounting, and thrusting increased significantly over castrate levels on postimplantation day 14 in the Bilateral group, but not in the Miss or Unilateral groups. In all groups, mean plasma testosterone concentrations were below or near the lower limit of detectability on the day before TP implantation and on postimplantation test days. In the same plasma samples, luteinizing hormone concentrations were within the normal range of castrated ferrets, and did not significantly decline after TP implantation. These results suggest that the MPOA is a neural site for androgen activation of certain components of reproductive behavior but not for negative feedback on gonadotropin secretion in male ferrets.

Animals

Effects of photoperiod and hypothalamic knife cuts on the timing of FSH surges in hamsters.

The timing of the proestrous surge of follicle-stimulating hormone (FSH) was examined in female hamsters with hypothalamic knife cuts that prevented reproductive responses to photoperiod. All animals received either a horizontal knife cut aimed between the suprachiasmatic nuclei (SCN) and the paraventricular nuclei (PVN), or sham surgery, and were housed in long (16 h of light/24 h) or short (6 h of light/24 h) photoperiods. Following exposure to either photo-period for 11-12 weeks, a subset of the animals was fitted with an indwelling jugular cannula. Blood samples were taken hourly over a 24-h period and plasma levels of FSH were determined by RIA. Knife cuts placed ventral to or through the ventral portions of the PVN prevented short day-induced anestrus. On the day of proestrus, peak elevations of FSH in cycling animals with knife cuts in both photoperiods, as well as in sham-operated females in long days, occurred 4-5 h before lights out. In contrast, sham-operated anestrous females in short days showed peak elevations of FSH approximately 3-4 h after lights out. The present results support the view that neural connections between the SCN and the PVN mediate the effects of short days on reproductive physiology, including changes in the timing of the FSH surge.

Animals

Pituitary responsiveness to luteinizing hormone-releasing hormone in prepubertal and postpubertal male ferrets.

The pituitary response to three different doses of exogenously administered LHRH was examined in prepubertal (9-wk-old) and postpubertal (32-wk-old) male ferrets. The doses of 5, 10, and 15 ng LHRH/kg body weight tested in this study produced dose-related increases in circulating LH concentrations in both pre- and postpubertal groups. In addition, a significant effect of age on LH response was observed, with the prepubertal animals demonstrating significantly greater serum LH values in response to the two higher doses than the postpubertal males. Prepubertal ferrets also exhibited a significant increase in endogenous LH pulse amplitude in sampling periods following exogenous administration of LHRH compared to baseline pulse amplitudes in periods prior to the LHRH infusions. These results suggest that the low frequency of endogenous LH pulses previously observed in prepubertal ferrets is not due to unresponsiveness of the pituitary gland to LHRH. Thus, suppression of the hypothalamo-hypophyseal axis observed in the prepubertal ferret is probably mediated at the level of the hypothalamus.

Aging

Photoperiodic regulation of gonadal growth and pulsatile luteinizing hormone secretion in male ferrets.

Testicular growth was monitored in male ferrets subjected to one of the following photoperiodic treatments begun at weaning (8 weeks of age): 8 hr light/day (short days), 18 hr light/day (long days), or short days followed by transition to long days at either 10, 12, or 14 weeks of age. Mean ages to achieve adult testis width of greater than or equal to 12 mm were 27.5 +/- 1.3, 25.0 +/- 1.5, 23.6 +/- 2.9, 20.0 +/- 0.8, and 21.2 +/- 1.0 weeks in ferrets raised from weaning in long days, raised from weaning in short days, and transferred from short to long days at 10, 12, or 14 weeks, respectively. This criterion was met significantly earlier by ferrets experiencing the photoperiod transition at 12 or 14 weeks of age than by ferrets housed in long days from weaning. At the end of the experiment (30 weeks of age), mean testis width was significantly smaller in ferrets raised in long days from weaning or transferred to long days at 10 weeks of age, compared to that of the other three groups (p less than 0.05). In a second experiment, photoperiod experience with long or short days was begun at birth, and testicular size was monitored for a longer period of time. The time courses for testicular maturation were similar to that obtained when these treatments began at weaning. By 40 weeks of age, mean testis width of ferrets raised in long days was comparable to that of ferrets raised in short days. A third study determined that the retarded testicular growth observed in ferrets exposed to long days from weaning was correlated with diminished pulsatile luteinizing hormone (LH) secretion. At 28 weeks of age, mean LH pulse frequency was 0.86 +/- 0.09 pulses/hr in ferrets undergoing spontaneous puberty in short days or photoinduced puberty after a short-to-long-day transition; pulse frequency was significantly lower (0.46 +/- 0.26 pulses/hr; p less than 0.05) in ferrets raised in long days. These results indicate that gonadal growth can be precociously induced in male ferrets by exposure to a sequence of short days followed by long days, and that the absence of sufficient prepubertal exposure to short days compromises pulsatile LH secretion and rate of gonadal growth. Experience with short days during development may be necessary for manifestation of stimulatory responses to long days.

Aging

Immunocytochemical localization of hypothalamic luteinizing hormone-releasing hormone in male ferrets.

LHRH-containing neurons within the hypothalamus were immunocytochemically identified in adult male ferrets that were either gonadally intact, castrated, or castrated and treated with testosterone. The distribution of LHRH-immunopositive neuron cell bodies was similar in the three treatment groups. The majority of these cells was located mediobasally in the retrochiasmatic area, including some within the ventrolateral aspects of the arcuate nucleus. These soma were associated with a dense basal LHRH fiber plexus which extended to the median eminence. A smaller number of cell bodies was found slightly more dorsal and lateral to the major concentration at the base and midline. Isolated LHRH perikarya were occasionally observed in dorsal areas of the hypothalamus. There were no differences in the mean total number of hypothalamic LHRH cell bodies identified in the three treatment groups. These results indicate that the documented negative feedback effects of testosterone on LH secretion in male ferrets are not the result of an alteration in the absolute number of neurons capable of synthesizing LHRH.

Animals

Differential effects of electrolytic and chemical hypothalamic lesions on LH pulses in rats.

Electrolytic lesions of the arcuate nucleus were made in anesthetized adult castrated male rats. Luteinizing hormone (LH) pulse frequency averaged 2.4 pulses/h in controls but declined to a mean of 0.5 pulses/h in rats with bilateral damage to the arcuate nucleus. Because these lesions also damaged the median eminence, we tested the possibility that this disruption of LH secretion was due to coincidental damage to fibers of passage projecting to median eminence. Axon-sparing chemical lesions of the arcuate nucleus were made by intracranial injections of N-methyl-DL-aspartate (NMA) in anesthetized adult castrated rats. Mean LH pulse frequency was 2.3 and 2.5 pulses/h in control and NMA-injected rats, respectively. NMA injections destroyed arcuate neuronal cell bodies and produced a proliferation of glial cells within the nucleus. There was no apparent difference in the immunocytochemical staining intensity and distribution of luteinizing hormone-releasing hormone (LHRH) fibers in median eminence in rats receiving NMA or sham injections. These results suggest that the disruptive effects of electrolytic lesions of the arcuate nucleus on pulsatile LH secretion are a result of coincidental damage to LHRH neuronal projections to the median eminence and that neuronal cell bodies within the arcuate nucleus are not necessary for normal pulsatile LH secretion in male rats.

Animals

Differential effects of testosterone, 5 alpha-dihydrotestosterone and oestradiol-17 beta on plasma concentrations of LH in castrated ferrets.

The biological activity of testosterone often depends on the conversion of testosterone within the target cell to an androgenic or oestrogenic metabolite. The purpose of this study was to compare the relative ability of testosterone and two of its metabolites, dihydrotestosterone (DHT) and oestradiol, to suppress LH secretion in castrated male ferrets. Castrated ferrets were treated with five different doses of steroid by implanting various numbers of s.c. silicone elastomer capsules packed with either testosterone, DHT or oestradiol. The lowest dose of oestradiol (0.1 mm capsule length/100 g body weight, mean estimated total release rate of 25 ng/day) significantly suppressed plasma concentrations of LH in castrated ferrets. Higher amounts of DHT (2.5 mm capsule length/100 g body weight, mean estimated total release rate of 88 ng/day) were required for a significant reduction in plasma concentrations of LH. Concentrations of LH were also significantly lowered by testosterone when administered at a 2.5 mm capsule length/100 g body weight; however, estimated total release rate was 312 ng/day from these capsules. The fact that oestradiol was more effective than DHT, and that DHT was more effective than testosterone in inhibiting LH secretion in castrated ferrets, suggests that in gonadally intact ferrets, testosterone may be converted to DHT or oestradiol within target cells that mediate steroid negative feedback on LH secretion.

Animals

Evidence that a decrease in testosterone negative feedback mediates the pubertal increase in luteinizing hormone pulse frequency in male ferrets.

Neuroendocrine mechanisms regulating luteinizing hormone (LH) secretion during puberty were investigated in intact male ferrets and ferrets castrated at 8 wk of age that received s.c. implants of either empty or testosterone-filled Silastic capsules. To synchronize puberty onset among individuals, ferrets were exposed to short days between 8 and 16 wk of age, and then transferred to long days. Testis growth began in intact ferrets soon after photoperiod transition. Blood samples were obtained at 11, 15, 19, and 23 wk of age. LH pulse frequency was low in intact ferrets at 11 and 15 wk of age (less than or equal to 0.27 pulses/h), but rose to 0.94 pulses/h by 23 wk of age. No age-related increase in LH pulse frequency was observed in untreated castrated ferrets. LH pulses were rare in testosterone-treated castrated ferrets at 11 and 15 wk of age; but by 23 wk of age, frequency rose to 0.33 pulses/h. Thus, testis maturation in ferrets is accompanied by a dramatic increase in LH pulse frequency. No steroid-independent developmental increase in LH pulse frequency occurs in castrated ferrets. Furthermore, doses of testosterone that prevent LH secretion in young castrated ferrets do not as effectively suppress LH pulses in older ferrets. These data suggest that a decrease in the efficacy of testosterone negative feedback mediates the pubertal rise in LH pulse frequency in male ferrets.

Animals

Neural pathways involved in the photoperiodic control of reproductive physiology and behavior in female hamsters (Mesocricetus auratus).

Female hamsters received horizontal knife cuts to investigate the role of hypothalamic connections in the photoperiodic control of female reproductive functions. Knife cuts placed ventral to or through the paraventricular nucleus (PVN), but dorsal to the suprachiasmatic nucleus (SCN), prevented photoperiod-induced acyclicity and uterine regression in animals maintained under a nonstimulatory photoperiod for 10 weeks. The animals were then ovariectomized and tested for lordosis behavior following subcutaneous injections of ovarian hormones to investigate the photoperiodic modulation of female sexual behavior. Animals exposed to a nonstimulatory photoperiod were less behaviorally sensitive to treatment with estradiol benzoate (EB) alone, but did not differ from animals maintained under a stimulatory photoperiod when EB was combined with progesterone. The effect of photoperiod and behavioral sensitivity to hormone replacement was independent of the surgical condition. The results are consistent with the hypothesis that dorsal projections from the SCN to the PVN mediate gonadal responses to short photoperiods. They also indicate that photoperiod-induced changes in behavioral sensitivity to gonadal steroids may be mediated by neural pathways distinct from those that mediate the gonadal changes.

Animals

Effects of food restriction and restoration on gonadotropin and growth hormone secretion in immature male rats.

This experiment concerned the changing patterns in secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and growth hormone (GH) under conditions of food restriction and subsequent catch-up growth. Weanling male rats were given either restricted (4 g food/day) or unrestricted access to food until 60 days of age. At this age, food-restricted rats weighed only 25% as much as rats fed ad libitum. Food restriction resulted in a dramatic decrease in the frequency of LH and GH pulses, and in the amplitude of GH pulses. It also slightly but significantly decreased mean blood levels of FSH (which was not secreted in a pulsatile manner in 60-day-old controls fed ad libitum). When restricted rats were given unrestricted access to food, frequency of LH and GH pulses and mean levels of FSH increased significantly and simultaneously within 2 days in half of the animals. Only an additional 8-10% of their body weight decrement was recovered at this time. After 10 days of food restoration, when restricted rats still weighed 50% less than controls, their secretory patterns of all three hormones were not significantly different from those of controls. Thus, recovery of gonadotropin and GH secretion was relatively rapid. Except for the quantitatively lesser impact of food restriction on FSH secretion, there was no evidence of any priorities in the secretion of the three hormones. Under conditions of rapid catch-up growth, the secretory patterns of LH, FSH, and GH appeared to develop simultaneously.

Animals

Pulsatile release of luteinizing hormone and testosterone in male ferrets.

The temporal organization of LH and testosterone secretion was examined in male European ferrets. Hormone levels were measured in frequent blood samples taken via an indwelling jugular cannula from sexually mature and castrated ferrets. Intact ferrets discharge LH and testosterone in discrete pulses, but the frequency and amplitude of these pulses vary within and between individual males. The average frequency of LH pulses was 1.14 +/- 0.25 pulses/h, with an amplitude of 1.59 +/- 0.23 ng/ml in 11 ferrets. Testosterone pulse frequency and amplitude were 0.62 +/- 0.04 pulses/h and 16.96 +/- 2.5 ng/ml, respectively. The frequency, amplitude, and duration of hormone pulses were similar during the light and dark phases of the light-dark cycle. LH and testosterone peaks were temporally coupled with LH pulses preceding testosterone pulses by 10-20 min. However, not all LH pulses evoked a rise in testosterone. Frequently, trains of 2 or more LH pulses gave rise to a single testosterone pulse. Castration provoked a rapid increase in the frequency of LH pulses, and the interpulse interval became strikingly uniform within hours after orchidectomy. The amplitude of LH pulses, in contrast, increased gradually over the first 6 postcastration days and then plateaued at about 4.5 ng/ml. These findings demonstrate that LH pulses constitute functionally important signals to the testis, as evidenced by temporally related increments in testosterone secretion. Moreover, distinct differences in the development of the postcastration rise in the frequency and amplitude of LH pulses suggest that testosterone operates via multiple mechanisms to regulate LH release in the adult male. Finally, this study emphasizes the utility of the ferret as an animal model to study neural determinants of LH release in the male.

Animals

Reproductive responsiveness to short photoperiod develops postnatally in male golden hamsters.

The development of the reproductive response to short photoperiod in golden hamsters was examined by monitoring testis size in hamsters that were either: raised on 14L:10D from birth; raised on 6L:18D from birth; or born on 14L:10D and transferred to 6L:18D at either 1, 2, 3, 4, 5, 6, 7, 9, or 12 weeks of age. Testis growth occurred between 3 and 7 weeks of age at similar rates in all groups. Testicular regression occurred in all groups exposed to short days; the time of regression depended on the age of the animals when they were first transferred to 6L:18D. Testicular regression began at about 10 weeks of age in all groups transferred to 6L:18D between birth and 5 weeks of age. In contrast, regression began at 11.2, 13.3, 15.6, and 18.2 weeks of age in hamsters transferred to 6L:18D at 6, 7, 9, and 12 weeks of age, respectively. These results suggest that the reproductive system of male hamsters is refractory to the inhibitory effects of short days on reproductive function until 5 to 6 weeks of age. Thereafter, exposure to short days initiates testicular regression in hamsters within 5 to 7 weeks.

Aging

LHRH in the ferret: pubertal decrease in the number of immunopositive arcuate neurons.

This study correlated a region-specific change in the number of luteinizing hormone-releasing hormone-immunopositive (LHRH+) neurons with pubertal development in male ferrets. There were 50% fewer LHRH+ cell bodies in the arcuate nucleus of peri- and postpubertal ferrets than in prepubertal ferrets; this significant decrease represented a 15% reduction in the overall number of LHRH+ neurons. Intracerebroventricular colchicine did not reveal additional numbers of LHRH+ neurons in the arcuate nucleus, indicating that the pubertal decrease in arcuate LHRH+ cell bodies was not due to rapid transport of peptide. These results suggest that LHRH of arcuate origin may inhibit release of LHRH via ultrashortloop negative feedback in prepubertal ferrets. Cessation of peptide production in half of the arcuate LHRH neurons at puberty could result in a reduction in this inhibitory signal that permits the pubertal increase in LHRH/LH release. Alternatively, LHRH of arcuate origin may have a nonpituitary role. In either case, these data provide evidence for heterogeneity of function among LHRH+ neurons.

Animals