Biomedical subjects

D C Collins

Publications and source records attributed to D C Collins.

At least 73 records · Page 4Linked to original sources

PubMed1986

Chronic gonadotropin-releasing hormone agonist treatment suppresses ovulation and sexual behavior in group-living female rhesus monkeys.

The sexual behavior of six adult rhesus females was observed with each of four males prior to, during, and following a 90 day treatment with 20 micrograms/day of a gonadotropin releasing-hormone (GnRH) agonist (WY-40972). All females ovulated, approached males and copulated during an untreated cycle. No ovulations occurred during agonist treatment and all females showed reduced sexual interest during the last 25 treatment days. Three females showed elevated estradiol and copulated during the first 10 days of agonist treatment, but never showed similar levels of estradiol or copulation during the rest of treatment. Within 34 days after agonist treatment, all females initiated proximity to males, copulated, and ovulated. All females became pregnant on their second ovulation after agonist treatment. This demonstration that inhibition of ovulation with a GnRH agonist decreased rhesus female sexual initiation, demonstrates the importance of ovarian hormones to female sexual motivation and suggests that the changes in human female sexual interest should be evaluated during the development of agonist-based contraceptives.

Animals↗

PubMed1986

Effects of Silastic progesterone implants on activity cycles and steroid levels in ovariectomized and intact female rats.

We have previously shown that although Silastic implants of progesterone reduce the amount of running of animals living in activity wheels, progesterone-treated animals continue to show periodic fluctuations or peaks in activity. We hypothesized that although progesterone treatment inhibited estrous cycles, ovaries of animals treated with Silastic implants of progesterone continued to secrete estradiol in amounts adequate to stimulate moderate levels of running. In the present study we tested this hypothesis by removing ovaries from progesterone-treated animals and comparing their running behavior and steroid levels to progesterone-treated animals who received sham ovariectomies. Although progesterone treatment significantly inhibited running activity, removal of ovaries in progesterone-treated animals further suppressed running activity. In addition, both estradiol and progesterone levels were significantly reduced following removal of ovaries in progesterone-treated animals. We conclude that although Silastic progesterone implants inhibit normal ovarian and estrous activity cycles, ovaries produce sufficient estradiol to stimulate running behavior.

Activity Cycles↗

PubMed1986

Prolactin and blood pressure responses to perphenazine in human subjects: comparison of the oral and intramuscular routes.

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr +/- SD) was significantly shorter (p less than 0.05) for the 5mg IM (1.7 +/- 0.4) than the oral (4.5 +/- 0.6) route. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 +/- 5.69) than the oral (5.12 +/- 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2 mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.

Administration, Oral↗

PubMed1986

Ontogeny of luteinizing hormone secretion and first ovulation in seasonal breeding rhesus monkeys.

A longitudinal analysis assessed the role of nongonadal control and estradiol (E2) inhibition of LH secretion during puberty in female rhesus monkeys and examined how maturational changes in LH release were related to GH secretion, ponderal growth, and seasonal changes in the environment. Three groups of spring-born monkeys housed outdoors were studied from 12 months of age in May 1982 through 43 months of age in December 1984: gonadally intact (INT; n = 8), ovariectomized (OVX; n = 5), and OVX E2 treated (E2OVX; n = 5; E2, approximately 45 pg/ml). Suppression of bioactive levels of LH by E2 was functional once changes in nongonadal control of LH release occurred, as basal LH levels increased significantly earlier in OVX (23.7 +/- 2.1 months) than either E2OVX (29.6 +/- 0.4 months) or INT (29.6 +/- 1.0 months). Although these increases in LH were not seasonally limited, higher levels were achieved if these initial increases occurred during the fall. Menarche in INT females occurred after the initial increases in LH (30.9 +/- 0.1 months). First ovulation for INT females was seasonally restricted, occurring either at 31.5 +/- 0.4 months in December/January (n = 3) or 11 months later at 42.5 +/- 0.4 months in October/November (n = 5). No ovulations occurred during the intervening spring and summer period, as serum levels of LH were significantly lower than in the preceding perimenarchial fall months. After the initial maturational increases, LH levels declined significantly in OVX and E2OVX females in late winter at 33 months before rising again the next fall. The timing and extent of the maturational decrease in E2 inhibition of LH secretion were related to developmental increases in serum GH and not to body weight. Furthermore, females who had a normal first ovulation shortly after menarche at 31 months had significantly higher serum GH levels yet similar growth rates and body weights compared to their age-mates. First ovulation at 43 months in the remaining females occurred after sustained elevations in serum GH, similar to those observed in the early ovulating females. These data indicate that both nongonadal control and steroid inhibition of LH secretion operate during puberty in female rhesus monkeys and support the hypothesis that the final stages of puberty are characterized by a maturational decrease in E2 negative feedback of LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1986

Treatment of endometriosis in monkeys: effectiveness of continuous infusion of a gonadotropin-releasing hormone agonist compared to treatment with a progestational steroid.

The use of a GnRH agonist or a progestational steroid (levonorgestrel) for the treatment of endometriosis in monkeys was compared. Four monkeys with spontaneous endometriosis were treated for 6 months with a continuous infusion of a GnRH agonist (25 micrograms/day). Five animals with surgically induced endometriosis were treated with the same agonist for 3 months. An additional group of five monkeys with surgically induced endometriosis was treated orally with levonorgestrel (1 mg/kg X day), while a final group of four monkeys served as untreated controls. During agonist treatment, the four monkeys with spontaneous endometriosis gained body weight and had a greater than 80% decline in cyst size (representing a decline in secretory activity). Monkeys with surgically induced endometriosis had almost total resolution of endometrial lesions during agonist treatment, which was maintained throughout a 4-month posttreatment period. After initial stimulation at the onset of the GnRH agonist infusion, serum LH, FSH, estradiol, and progesterone levels decreased to near the levels of detection, where they remained until treatment was terminated. In comparison, levonorgestrel reduced endometrial lesion size, but the monkeys did not resume normal cycles as early as those treated with the agonist. Levonorgestrel-treated monkeys had normal serum LH and FSH levels, but low serum estradiol and progesterone levels. The results of this study indicate that either continuous infusion of a GnRH agonist or administration of levonorgestrel is effective for treating endometriosis in monkeys. The hormonal data suggest that the GnRH agonist acts at the level of the hypothalamus and pituitary, whereas levonorgestrel acts at the ovarian level.

Animals↗

PubMed1986

Influence of acute intracerebroventricular (i.c.v.) administration of adrenocorticotrophin (ACTH) on LH secretion in male rats: effect of pretreatment (i.c.v.) with ACTH antiserum on the serum LH response to an acute ether stress.

Adult male rats with chronic indwelling intracerebroventricular (i.c.v.) and jugular catheters were given an i.c.v. injection (over 1 min) of 1, 10, 100 ng or 1 microgram ACTH(1-24), or 300 ng ACTH(4-10) or saline, and blood samples were taken 0, 5, 15, 30 and 60 min later. Increasing dosages of ACTH(1-24) caused a dose-related rise in serum LH levels. Peak levels of serum LH (ranging from 157 to 473% of pretreatment levels) were reached 5-15 min after treatment, and then serum LH values returned to pretreatment levels by 60 min. The serum LH response to 1 microgram ACTH(1-24) did not differ from the response to 100 ng ACTH(1-24). Administration (i.c.v.) of 300 ng ACTH(4-10) was also effective in increasing serum LH values. Repeated withdrawal of blood during the experiment increased serum corticosterone values in all groups (including saline-treated), but i.c.v. administration of ACTH(1-24) or ACTH(4-10) did not further increase serum corticosterone levels. Two additional groups of rats were injected i.p. with either saline or pentobarbital (30 mg/kg body weight) 1 h before i.c.v. administration of 10 ng ACTH(1-24) and blood samples were taken as in the other groups. The animals in these groups did not show a rise in serum LH concentrations in response to ACTH(1-24). In a third experiment, rats were pretreated (i.c.v.) with either ACTH antiserum (ACTH-Ab) or normal rabbit serum 15 min before a 2-min ether stress. The ether stress evoked a significant rise in serum LH concentrations within 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1985

The inhibitory effect of caffeine on hormone-induced rat breast cancer.

Studies have associated coffee and/or caffeine with human fibrocystic breast disease. Two animal studies have implicated caffeine as a promoter in rat mammary cancer. The current investigation examines the effect of two caffeine doses in ACI rats with and without diethylstilbestrol (DES). Without DES, cancer did not develop in any of the rats receiving either of the two caffeine dosages. With DES, increasing caffeine dosage lengthened the time to first cancer, decreased the number of rats that developed cancers, and decreased the number of cancers overall. The presence or amount of caffeine did not cause detectable histologic differences in the breast cancers. The presence or amount of caffeine did not influence animal weight or mortality, although the rats without DES weighed more and survived better into old age. The presence or amount of caffeine did not influence pituitary weights and prolactin levels, although values of the DES groups were three times higher than the values for the group without DES (P less than 0.05). In conclusion, chronic caffeine ingestion inhibits rat breast cancer, neither by interfering with the high prolactin levels--a necessary step in murine tumor development--nor by causing hypocaloric intake.

Animals↗

PubMed1985

Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone and testosterone secretion and testicular histology in male rhesus monkeys.

Three adult male rhesus monkeys were treated for 20 weeks with a gonadotropin-releasing hormone (GnRH) agonist (Ag; Wy-40972; Wyeth Laboratories, Philadelphia, PA) using osmotic minipumps. Ag administration resulted in a transient increase and then a precipitous decrease in the concentration of luteinizing hormone (LH) and testosterone (T). After 5 weeks, serum levels of LH were undetectable (less than 0.2 microgram/ml), while serum T was always detectable, but continued to fall throughout the period of Ag administration. The serum LH and T response to 50 micrograms of GnRH was abolished by 4 weeks of Ag treatment, and this effect persisted through the treatment period. Testicular histology at 20 weeks of Ag treatment exhibited diffuse atrophy of seminiferous tubules, suppressed germinal cell division, and the absence of spermatids or spermatozoa. There was no evidence of testicular necrosis or calcification of the seminiferous tubules. Following the termination of Ag infusion, serum LH and T concentrations rebounded to levels that exceeded pretreatment values for a 5-week period before falling back to baseline levels. A complete restoration of spermatogenesis and testicular volume occurred by 12 weeks after treatment. These data suggest that continuous Ag administration is an effective method of reversibly disrupting spermatogenesis in the male rhesus monkey.

Animals↗

PubMed1985

Reproductive biology of paraplegics: results of semen collection, testicular biopsy and serum hormone evaluation.

The fertility and urological status of 30 male paraplegics between 20 and 47 years old with lesions between the T2 and L3 levels were examined by studying serum hormone levels (estradiol-17 beta, testosterone, prolactin, and follicle-stimulating and luteinizing hormones), sperm and semen characteristics via testicular biopsy and rectal probe electrostimulation, and urodynamic evaluation. Of the patients 13 had reflexic, 4 hyperreflexic and 13 areflexic bladders. Nine of the 13 patients with reflexic and all 4 with hyperreflexic bladders had a positive external sphincter electromyogram with detrusor-sphincter dyssynergia. When catheters were not used to collect semen during rectal probe electrostimulation, retrograde semen flow into the bladder was the rule. A total of 22 patients could tolerate rectal probe electrostimulation, while 6 who could not were injured at the T12 level or lower. Seminal emissions were obtained from 35 to 42 studies in these 22 patients. Total sperm count was variable; in 22 studies it was greater than 20 million. Progressive motility usually was low; 77 per cent of the patients had less than 20 per cent motility. Of 13 biopsy specimens obtained 6 suggested normal testicular morphology, with tubule atrophy and spermatogenic activity only mildly reduced in 6 of the remaining 7. Serum testosterone and luteinizing hormone values were significantly higher (p less than 0.05) among the paraplegic patients than among intact male volunteers of the same age range. Other serum hormone levels were unchanged. Outcome of rectal probe electrostimulation and biopsy did not relate to the number of years of patient injury. Thus, the principal deterrent to the use of semen collected by rectal probe electrostimulation from paraplegics for artificial insemination resides in a predominantly low sperm motility. Suggestions for improvement of motility include 1) great care to minimize or prevent urinary tract infections, 2) selection of medications for urinary tract care that do not compromise sperm survival and 3) prevention of sperm stagnation in lower tract storage sites, perhaps by use of periodical rectal probe electrostimulation.

Adult↗

PubMed1985

Resumption of seasonal breeding patterns in male and female rhesus monkeys transferred from an indoor to an outdoor environment.

Seasonal aspects of social behavior and sex steroid levels were observed in two groups of rhesus monkeys from March through December. One group (3 males, 7 females) had lived outdoors for several years. The other group (6 males, 5 females), transferred outdoors in late February, had lived indoors for several years. In March-April, the long-term outdoor residents displayed the expected seasonal pattern of sexual behavior, characterized by absence of complete sequences of copulatory behavior. At this time the indoor-adapted group displayed high levels of copulatory behavior. Thereafter, frequencies of sexual behavior of the two groups were similar. Testosterone in the males was positively correlated with frequency of sexual behavior in each group. Females in the indoor-adapted group displaced menstrual cycles in March and April and 3 of 5 became pregnant at this time. The two remaining indoor-adapted females continued to display ovulatory cycles, but little sexual behavior, throughout the summer. Interestingly, two females in the outdoor-adapted group also displayed summer ovulatory cycles; without concomitant sexual activity. These data show that the disruption of seasonal breeding patterns produced by lengthy indoor housing remains briefly apparent following transfer outdoors, but is substantially overcome within a few months.

Agonistic Behavior↗

PubMed1985

Preliminary report on the use of fetal tissue transplantation to correct MPTP-induced Parkinson-like syndrome in primates.

A Parkinson-like syndrome was produced in nonhuman primates and successfully reversed through transplantation of heterologous fetal mesencephalic brain tissue. Rigidity and bradykinesia were induced by the chronic administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Once the deficits were fixed, Macaca mulatta with well-developed Parkinson-like behavior received fetal mesencephalic cell preparations stereotactically implanted into multiple sites of the head of the caudate bilaterally. Both animals demonstrated a normalization of CSF L-dopa and significant improvement in observed activity. The neuropathological studies performed 2 months following transplantation demonstrated successful integration of fetal cells in the caudate.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1985

Negative feedback effects of oestradiol-17 beta on luteinizing hormone in female rhesus monkeys under different seasonal conditions.

Suppression of luteinizing hormone (LH) by sc implanted oestradiol-17 beta (E2) pellets was examined in 4 ovariectomized female rhesus monkeys during the breeding season, the non-breeding season and during the transition between the breeding and non-breeding season. Immunoreactive LH was suppressed to 58, 78 and 75% of untreated levels for the respective seasonal conditions. Bioactive LH was suppressed to 29, 49 and 33% of baseline. Bioactive LH (determined by testosterone release from rat interstitial cells) was significantly correlated (r = 0.84) with immunoactive LH from the same samples. It is concluded that E2 treatment of ovariectomized female rhesus monkeys results in suppressed levels of LH, regardless of the time of year.

Animals↗

PubMed1984

Comparative effects of tamoxifen and bromocriptine on prolactin and pituitary weight in estradiol-treated male rats.

Male ACI rats were treated with estradiol to induce hyperprolactinemia and pituitary hypertrophy and hyperplasia. Animals received estradiol alone or with tamoxifen or bromocriptine for 4, 8, or 12 weeks. Estradiol treatment resulted in time-dependent increases in pituitary wet weight and serum prolactin concentrations. Tamoxifen completely blocked the increase in both variables; bromocriptine decreased but did not prevent time-dependent increases. Animals were also treated for 8 weeks with estradiol alone, followed by 4 weeks with estradiol and tamoxifen or bromocriptine. Neither compound reversed the hyperprolactinemia, although the pituitary wet weight of animals treated with bromocriptine was slightly but significantly reduced. These findings suggest that in this model if treatment is initiated simultaneously with estrogen stimulation, tamoxifen is more effective than bromocriptine at the doses studied; and, if therapy is initiated subsequent to the establishment of estrogen-induced hyperprolactinemia and pituitary hyperplasia, bromocriptine is more effective than tamoxifen at the doses studied.

Animals↗

PubMed1984

Periovulatory changes in female sexual behavior and patterns of ovarian steroid secretion in group-living rhesus monkeys.

The behavior of nine intact group-living adult female rhesus was observed for 30 min daily with each of four adult male rhesus across a verified ovulatory menstrual cycle. Blood samples collected from females daily or on alternate days were analyzed for estradiol, testosterone, and progesterone. Female patterns of approach, follow, and initiate proximity increased several days prior to the estradiol peak, peaked on the day of the estradiol peak, then declined completely or to very low frequencies. Mounts, intromissions, and ejaculations increased significantly on the day of the estradiol peak, remained elevated for 2 more days, then declined completely by the fifth day after peak estradiol. Ejaculations never occurred outside of a 10-day period starting 4 days before the estradiol peak and ending 5 days after the estradiol peak. During this period females initiated over 90% of all approaches. Female hand slap, threaten away, and stand up increased significantly on the first day of increased copulation, remained elevated while copulation was significantly elevated, then decreased along with the decline in copulation. Ten of eleven patterns of female behavior correlated significantly with estradiol level prior to the estradiol peak. All were significantly inversely correlated with progesterone level after the estradiol peak. No pattern of female behavior correlated significantly with testosterone either before or after the estradiol peak. Similarly, male patterns of behavior correlated with female levels of estradiol and progesterone, but not testosterone. These results demonstrate a relationship between increased serum estradiol and increased female initiation of sexual behavior. The finding that some patterns of female behavior increase several days prior to copulation, whereas other behaviors increase coincident with increased copulation suggests that the behavior of group-living rhesus females serves two functions. The first is to communicate sexual interest and the second is to maintain the consort pair and increase the probability that ejaculation will occur. In addition, the strong correlation between preovulatory female behavior and estradiol level suggests that the female's behavior provides precise information about her reproductive state and could thus coordinate copulation with maximal fertility.

Animals↗

PubMed1984

Endocrine changes induced by venipuncture in rhesus monkeys.

An animal-worn, remotely activated blood collection device was used to obtain estimates of baseline levels of testosterone (T), growth hormone (GH) and prolactin (PRL) from unrestrained and active male rhesus monkeys. As soon as possible after this baseline period, the males were captured and a final venipuncture sample was obtained. Venipuncture produced elevated GH levels compared to values obtained using the blood collection device, but was without detectable effect upon levels of T and PRL. Cortisol values, available only from a single animal, displayed an increase in response to venipuncture, much like that seen for GH.

Animals↗

PubMed1984

The role of beta-endorphins and catechol estrogens on the hypothalamic-pituitary axis in female athletes.

Competitive swimmers were followed over a 2-year period when they trained at different levels of exercise which coincided with distinct changes in their menstrual history. Oligomenorrhea was identified in 5 of 13 of these athletes when they swam approximately 100,000 yards per week. Weight and percentage of body fat were not significantly different between the period of oligomenorrhea and regular menstrual function (P = 0.24). Mean and median levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and 17beta-estradiol were decreased and catechol estrogens and beta-endorphins were increased in serum during the strenuous, when compared with the moderate, training period. The serum levels of the steroid and protein hormones were similar to those of normal cycling, nonexercising control subjects during moderate exercise (60,000 yards per week). The significant differences between beta-endorphins and catechol estrogens during periods of strenuous exercise suggest an explanation for oligomenorrhea in female athletes. These hormonal changes result in hypothalamic anovulation, which appears to be reversible, because the hormone levels and menstrual cycles return to normal when the exercise is reduced.

Adolescent↗

PubMed1984

Influence of continuous gonadotropin-releasing hormone (GnRH) agonist treatment on luteinizing hormone and testosterone secretion, the response to GnRH, and the testicular response to human chorionic gonadotropin in male rhesus monkeys.

Five adult male rhesus monkeys were continuously infused for 56 days with 25 micrograms/day of GnRH agonist (Wy-40972; Ag) using an implanted osmotic pump. Bioassayable serum levels of LH were elevated 8-fold on the second day of Ag treatment and then declined precipitously to below pretreatment levels by day 15. Serum levels of testosterone (T) changed similarly during Ag treatment, except that the fall in serum LH levels preceded the decline in serum levels of T by at least 2 days. Ag administration also eliminated the diurnal variation in serum LH and T. GnRH administration (50 micrograms) induced a 13- to 20-fold rise in serum LH and a 3- to 7-fold increase in serum T in control monkeys. After 4 weeks of Ag administration , none of the animals responded to GnRH. Both control and experimental monkeys had a rise in serum T in response to hCG after 7 weeks of Ag treatment. Basal levels of LH and T returned to normal by 12 days posttreatment, and the serum LH and T responses to GnRH were normal 19 days posttreatment. These results indicate that 1) continuous administration of Ag is an effective method of inducing antiferility effects in male rhesus monkeys; 2) pituitary desensitization is a major factor involved in Ag-induced gonadal dysfunction in this species; and 3) the method of administration may be the critical factor in determining the effectiveness of GnRH agonists.

Animals↗

PubMed1984

Blockade of neonatal activation of the pituitary-testicular axis with continuous administration of a gonadotropin-releasing hormone agonist in male rhesus monkeys.

The objective of this study was to determine the effects of continuous GnRH agonist (Ag) treatment on neonatal activation of the pituitary-testicular axis in male rhesus monkeys. Five infants were treated continuously with Ag(10 micrograms/day; Wy-40972) for 112 days using osmotic minipumps beginning at 10-13 days of age. Two of five age-matched control animals were implanted sc with Silastic implants of comparable size to the minipumps; three did not receive sham implants. Ag treatment caused a fall in serum LH (bioassay) values to undetectable levels (much less than 0.1 micrograms/ml) within 3 weeks, where they remained throughout Ag treatment. Mean serum testosterone (T) levels fell from pretreatment values of 1.52 +/- 0.45 to 0.38 +/- 0.09 (+/- SE) ng/ml after 3 weeks of Ag treatment. The level of T never exceeded 0.60 ng/ml throughout the subsequent course of Ag treatment. In contrast, serum LH and T were elevated to levels that approached adult values during the first 2 postnatal months in control infants with or without sham implants. Both LH and T then gradually declined, and by 4 months of age, T levels were indistinguishable from those in Ag-treated animals. Control infants had an increase in serum LH from 0.56 +/- 0.10 to 2.67 +/- 0.49 micrograms/ml within 60 min of administration of 5 micrograms GnRH/kg BW at 60 days of age. Serum T values rose from 2.35 +/- 1.00 to 9.48 +/- 3.15 ng/ml during the same period. Seven weeks of Ag treatment abolished the LH and T responses to GnRH. Thirty days after the termination of Ag treatment (approximately 150 days of age), Ag-treated and control infants had comparable serum LH and T responses to GnRH, although the responses were reduced relative to the responses in controls at 60 days of age. These results suggest that continuous administration of Ag desensitizes the pituitary of the male infant rhesus monkey to GnRH and blocks neonatal activation of the pituitary-testicular axis.

Aging↗