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D C Collins

Publications and source records attributed to D C Collins.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effects of a gonadotropin-releasing hormone agonist on sexual behavior in male rhesus monkeys (Macaca mulatta).

Low levels of sexual behavior persist in male rhesus monkeys treated with GnRH-a despite very low levels of T and gonadotropin that occur during such treatment. The behavior of male rhesus monkeys treated with GnRH-a resembles the behavior of surgically castrated male rhesus monkeys more closely than it does the behavior of reproductively quiescent males during the normal nonmating season. The normal, seasonal cessation of sexual behavior in male rhesus monkeys may result from changes in behavioral sensitivity to circulating androgens.

Animals↗
PubMed1989

The effect of naloxone and metoclopramide on the hypothalamic pituitary axis in oligomenorrheic and eumenorrheic swimmers.

Eight highly competitive swimmers were followed over a 9-month period during a vigorous training schedule. When compared, four oligomenorrheic (group I, greater than 60 days without menses) and four eumenorrheic (group II) swimmers were not significantly different for age, years of training, body fat, intensity of training, and baseline estradiol (E2) levels. Both groups were challenged during the peak of their training schedule with 10 mg of naloxone and 10 mg of metoclopramide. The naloxone infusion revealed a significant increase in baseline luteinizing hormone (LH) levels in the oligomenorrheic swimmers when compared with the eumenorrheic swimmers. During the metoclopramide infusion prolactin (PRL) increased in all subjects, with a slightly higher increase in PRL in the eumenorrheic swimmers. The study suggests the menstrual dysfunction observed in these strenuously training swimmers to be related to the abnormalities of endorphin physiology as revealed by the elevation in LH after a naloxone infusion.

Adolescent↗
PubMed1989

Blockade of neonatal activation of the pituitary-testicular axis: effect on peripubertal luteinizing hormone and testosterone secretion and on testicular development in male monkeys.

The objective of this study was to examine the effect of blockade of neonatal activation of the pituitary-testicular axis, using a GnRH agonist, on sexual development in male rhesus monkeys. Monkeys were treated with either a GnRH agonist (10 micrograms/day; n = 8) or vehicle (n = 9) for 112 days using osmotic minipumps beginning at 10-13 days of age. In control monkeys serum LH and testosterone concentrations during the first 3 postnatal months were similar to those in adults; they then declined to very low levels. GnRH agonist administration caused an immediate and precipitous decline in serum LH and testosterone concentrations to very low levels, and both remained low throughout the rest of the agonist administration period. Neither group had any significant elevation in serum LH or testosterone concentrations during the next 2 yr. In the control monkeys serum LH and testosterone began to rise during the third year, with a rapid increase occurring during the fall coincident with the breeding season. This peripubertal rise of LH and testosterone secretion was associated with rapid enlargement of the testes and the appearance of sperm in ejaculates. The monkeys who had received GnRH agonist had subnormal serum LH and testosterone increases, and testicular enlargement was also attenuated compared to that in the control animals during the third year of life. Semen samples were recovered from only 50% of the GnRH agonist-treated monkeys during this period, and the sperm count per ejaculate was suppressed. The serum LH responses of the GnRH agonist-treated monkeys to an iv bolus dose of GnRH (5 micrograms/kg BW) during the third year were normal. These results suggest that the induction of reversible hypogonadotropin-hypogonadism in neonatal male monkeys alters subsequent testicular development and peripubertal endocrine changes. Thus, neonatal activation of the pituitary-testicular axis may be a critical developmental event in the process of sexual development in male primates.

Animals↗
PubMed1989

Evaluation of the possible direct effects of gonadotrophin-releasing hormone analogues on the monkey (Macaca mulatta) testis.

In Exp. 1, the effect of treatment with a GnRH agonist on basal concentrations of serum testosterone and peak values of serum testosterone after administration of hCG was determined. One group of adult male monkeys was treated with a low dose (5-10 micrograms/day) and a second group with a high dose (25 micrograms/day) of a GnRH agonist for 44 weeks. Basal and peak testosterone concentrations were both significantly reduced by GnRH agonist treatment in all groups compared to untreated control animals, but the % rise in serum testosterone above basal values in response to hCG administration was unchanged by agonist treatment. In Exp. 2, the GnRH agonist (100 or 400 ng) or a GnRH antagonist (4 micrograms) was infused into the testicular arteries of adult monkeys. The agonist did not alter testosterone concentrations in the testicular vein or testosterone and LH values in the femoral vein. In Exp. 3, testicular interstitial cells from monkeys were incubated with three concentrations (10(-9), 10(-7) and 10(-5)M) of the GnRH agonist or a GnRH antagonist with and without hCG. After 24 h, neither basal nor hCG-stimulated testosterone production was affected by the presence of the GnRH agonist or antagonist. The results from all 3 experiments clearly suggest that GnRH agonist treatment does not directly alter steroid production by the monkey testis.

Animals↗
PubMed1988

Dietary influences on growth and sexual maturation in premenarchial rhesus monkeys.

The effect of a high-fat diet on growth, sexual maturation, and developmental changes in serum levels of estradiol (E2), growth hormone (GH), somatomedin-C (Sm-C), and insulin were examined in outdoor-housed premenarchial rhesus monkeys. From 16 to 32 months of age, females were fed either a high-fat diet (HFD, N = 5) with 31% calories from fat or a control diet (commercial laboratory chow, N = 10) with 12% of the calories from fat. Maintenance on a HFD did not accelerate physical growth, as all animals exhibited similar increments in body weight, crown-rump length, and weight/height ratios. In contrast, the HFD group exhibited an earlier onset of perineal swelling and menarche despite lower body weights during that time. Moreover, 80% of the HFD animals exhibited an early first ovulation (31-32 months of age) compared with 40% of control animals. These reproductive changes were associated with significant differences in the endocrine profiles of HFD animals. Fasting serum levels of insulin were significantly elevated within 2 months of diet treatment and remained elevated throughout the study period. Levels of Sm-C were elevated relative to those of controls after 3 months of diet treatment, but not thereafter. Serum GH increased after 6 months on the HFD and, overall, concentrations were higher in HFD animals. A significant rise in E2 was observed after only 45 days on the HFD treatment. These concentrations did not differ from 18 to 21 months of age but again were elevated at 27 months in the HFD females. Since these endocrine and physical changes associated with reproductive physiology occurred in the absence of enhanced growth, these data suggest that a high-fat diet may influence the rate of sexual maturation through changes in certain metabolic factors which may act on the developing neuroendocrine system.

Animals↗
PubMed1987

Long-term effect of a first pregnancy on the secretion of prolactin.

An early first pregnancy is known to protect against subsequent breast cancer. We speculated that this effect may be mediated by a long-term depression of prolactin secretion after pregnancy. We therefore measured basal and post-stimulation serum levels of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in two groups--15 women 18 to 23 years of age and 9 women 29 to 40--before and after a first full-term pregnancy, and in 40 appropriate nulliparous controls. We observed no significant change in basal levels of serum LH or FSH or in the levels stimulated by gonadotropin-releasing hormone in any group. A significant decrease was seen, however, in basal and perphenazine-stimulated levels of prolactin after pregnancy in both the younger and older first-pregnancy groups but not in the controls. In a separate cross-sectional study, we compared basal serum prolactin levels in 29 parous and 19 nulliparous women of similar age. The serum prolactin levels were significantly lower in the parous group but were not related to the number of pregnancies (one to three) or the time elapsed (12 to 150 months) since the last delivery. We conclude that a first pregnancy leads to a long-term decrease in serum prolactin secretion, lasting at least 12 to 13 years.

Adolescent↗
PubMed1987

Silent ovulation in rhesus monkeys (M. mulatta): dissociation of hormonal and behavioral states.

Ovarian hormone levels were monitored in rhesus monkeys during the breeding and non-breeding seasons. Ovulation (as inferred from progesterone levels in blood serum in excess of 1.5 ng/ml) was most frequent in the breeding season but was absent only during the month of August. Summer (non-breeding season) ovulations were more frequently "silent," or without heterosexual behavior, than were winter ovulations. This finding suggested that estradiol stimulation may cause different behavioral responses at different times of the year. To test this hypothesis, ovariectomized females were treated with subcutaneously implanted estradiol capsules at different times within and outside the normal breeding season. In either season, treatment with estradiol resulted in increased female-to-female sexual behavior. Only during the breeding season, however, did the estradiol-treated ovariectomized females interact sexually with males. Although males copulated with both estradiol-treated and gonadally intact, untreated females during the breeding season, their rate of copulation with the intact females was higher. The results suggest that: (1) Some female rhesus monkeys displaying strictly seasonal breeding behavior continue to have luteal activity indicative of ovulation in May, June and July, (2) Summer ovulatory cycles are rarely accompanied by sexual behavior, (3) Estradiol treatment of ovariectomized females induces female-to-female sexual behavior both in the breeding and non-breeding seasons, and (4) Males are less responsive to the presence of estrogen-stimulated females in the non-breeding season than in the breeding season.

Animals↗
PubMed1987

Age-related changes in the female hormonal environment during reproductive life.

Previous studies have indicated that serum levels of follicle-stimulating hormone rise with age during the female reproductive life, but the effect on other hormones is not clear. We studied the effects of age, independent of pregnancy, by comparing serum hormone levels in two groups of nulliparous, premenopausal women aged 18 to 23 and 29 to 40 years. We found that increased age during reproductive life is accompanied by a significant rise in both basal and stimulated serum follicle-stimulating hormone levels. This was accompanied by an increase in the serum level of estradiol-17 beta and the urine levels of estradiol-17 beta and 17 beta-estradiol-17-glucosiduronate. The serum level of estrone sulfate decreased with age. Serum and urine levels of other estrogens were unchanged. The basal and stimulated levels of luteinizing hormone were also unchanged. There was a significant decrease in basal and stimulated serum prolactin levels. Serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate decreased with age, but serum testosterone was unchanged. It is concluded that significant age-related changes in the female hormonal environment occur during the reproductive years.

Adolescent↗
PubMed1987

Serum levels of cholesterol and lipoproteins in rhesus monkeys: comparison of the effect of gonadotropin-releasing hormone agonist and the progestin, levonorgestrel.

Levonorgestrel, a progestational steroid, and the more widely used antigonadotropin, danazol have been used in the treatment of endometriosis. Both of these agents decrease serum levels of HDL cholesterol. Recently, GnRH agonists came into use for treatment of endometriosis. Our objective in this study was to compare the effects of levonorgestrel and a GnRH analog on serum cholesterol levels in rhesus monkeys being treated for surgically induced endometriosis. A high dose of levonorgestrel significantly reduced total serum cholesterol and HDL cholesterol during a 12-week treatment period. Levonorgestrel had no significant effects on the concentration of LDL/VLDL cholesterol or the percentage of total cholesterol in the HDL fraction. Conversely, the GnRH agonist had no significant effect on total serum cholesterol, HDL cholesterol, LDL/VLDL cholesterol, or the percentage of HDL cholesterol. Because the concentration of HDL cholesterol is closely correlated with atherosclerotic risk, this factor should be weighed in the overall risk/benefit analysis for the patient with endometriosis.

Animals↗
PubMed1987

Beta-endorphin-induced hyperglycemia in rabbits: effects of a glucose or arginine challenge.

The effects of beta-endorphin on glucose, insulin, and glucagon levels were studied in normal fasted adult male rabbits. An intravenous bolus of glucose (0.7 g/kg body wt) produced a hyperglycemic state (peak plasma glucose 306 +/- 22 mg/dl; means +/- SE) that lasted approximately 90 min. beta-Endorphin (31 micrograms/g body wt; iv) administered immediately prior to the glucose challenge resulted in plasma glucose levels that were significantly higher from 10 to 90 min after the glucose challenge (P less than 0.001-0.05). From 10 to 30 min, plasma insulin levels were significantly lower in the beta-endorphin group (P less than 0.001-0.05), peaking at one-half the control group levels. Glucagon levels were unchanged by the glucose bolus in either the control or beta-endorphin-treated group (means +/- SE = 102.8 +/- 4 pg/ml). In another experiment, a 30-min infusion of L-arginine (13 mg-1 X kg body wt-1 X min iv) in normal fasted rabbits produced a rapid (10 min) increase in plasma insulin and glucagon and a return to base-line levels 60 min after withdrawing the arginine stimulus. Plasma glucose levels were not altered by arginine (mean +/- SE = 94.5 +/- 1 mg/dl). Administration of beta-endorphin (31 micrograms/kg body wt iv) at the start of the arginine infusion resulted in a rapid (10 min) and long-lasting (up to 60 min) hyperglycemic effect associated with a significant decrease in insulin levels (10-20 min; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Mutually independent effects of adrenocorticotropin on luteinizing hormone and testosterone secretion.

In this study, we examined the effect of ACTH on the sensitivity of the testes to gonadotropin and determined the role of the testosterone (T) negative feedback system in mediating the inhibitory effect of ACTH on LH secretion in adult male rats. ACTH infusion for 3 days reduced basal levels of serum T and the T response to GnRH, but did not alter basal levels of serum LH (immunoreactive) or the LH response to GnRH. These effects required the presence of the adrenal glands. Infusion of corticosterone (B) at a dose that increased serum B concentrations 9-fold had an effect similar to that of ACTH on basal serum T levels and the serum T response to GnRH. Basal levels of serum LH and the serum LH response to GnRH were not affected by B administration. These data suggest that ACTH administration reduces the sensitivity of the testes to LH, resulting in a lower basal level of T and a reduced T response to GnRH. This effect was independent of basal serum LH levels or the LH response to GnRH. It appears that B mediates the effect of ACTH on testicular sensitivity to gonadotropin. In another experiment, ACTH administration for 4 days did not alter serum LH values, but reduced serum T levels in sham-castrated male rats. In contrast, ACTH treatment blunted the increase in serum LH after castration by day 2 of treatment, despite the absence of detectable levels of serum T within 6 h after castration. These data suggest that T is not essential for the inhibitory effect of ACTH on LH secretion to occur. They do not support the hypothesis that ACTH enhances the sensitivity of the hypothalamus and/or pituitary to the negative feedback effects of T.

Adrenalectomy↗
PubMed1987

Long term effects of a first pregnancy on the hormonal environment: estrogens and androgens.

An early (but not a late) first pregnancy is known to be protective for breast cancer. This effect might be mediated through a long term change in the hormonal environment caused by the early first pregnancy. To investigate the possibility of such a change we carried out a prospective longitudinal study of serum and urinary estrogens and serum androgens in four groups of women, namely early (age, 18-23 yr) first pregnancy (n = 15), early control (n = 20), late (age, 29-40 yr) first pregnancy (n = 9), and late control (n = 20). The pregnancy groups were studied before (initial visit) and 7-19 months after a first pregnancy (return visit). The control groups were similarly studied, but without an intervening pregnancy. The following were measured: serum estrone (E1), 17 beta-estradiol (E2), estriol (E3), and E1 sulfate; urinary total E1, E2, E3, and glucosiduronates of these three estrogens; and serum testosterone, dehydroepiandrosterone sulfate (DHAS), and dehydroepiandrosterone (DHA). There was no significant change between the initial and return visits in serum E1, E2, E1 sulfate, or any of the urinary estrogens in either pregnancy group or in the corresponding control groups. There was, however, a significant increase in serum E3 between initial and return visits for both pregnancy groups compared with the control values. There was no significant change in serum testosterone. There was a marked significant decrease in both serum DHAS and DHA between initial and return visits in both pregnancy groups compared with the corresponding control group values. There was also a significant increase in the serum E3 to DHA ratio in both pregnancy groups. A cross-sectional study (measuring serum DHAS and DHA only) was then carried out in a series of parous and nulliparous women. The serum DHAS and DHA levels were markedly and significantly lower in parous than in nulliparous women, as expected. There was no significant relationship between serum DHAS or DHA levels and months elapsed (up to 150) since last delivery, indicating that the changes last at least for this period of time. There was no significant relationship between serum DHAS or DHA levels and parity (one to three previous pregnancies), indicating that the changes occur only after a first pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Effect of diet on oxidation of 17 beta-estradiol in vivo.

The effect of a high fat, low carbohydrate, low protein diet on the in vivo oxidation of 17 beta-estradiol was studied using radiometric methods. Five male chimpanzees were fed a normal (13%) fat diet or a high (65%) fat diet for 8 weeks. After a 4-week rest period, the animals were fed the alternative diet. The mean percent oxidation of 16 alpha-[3H]estradiol-17 beta 24 h after injection was 3.8 +/- 1.3% (+/- SD) on the normal diet vs. 18.4 +/- 4.7% on the high fat diet (P less than 0.01). In contrast, the mean percent oxidation of 2-[3H]estradiol 24 h after injection was 31.6 +/- 3.8% (+/- SD) on the normal diet vs. 20.0 +/- 3.5% on the high fat diet (P less than 0.05). These results suggest that the oxidation of 17 beta-estradiol to estriols relative to that to catechol estrogens is increased by a high fat diet.

Animals↗
PubMed1987

Influence of simultaneous gonadotropin-releasing hormone agonist and testosterone treatment on spermatogenesis and potential fertilizing capacity in male monkeys.

We examined the effect of continuous sc infusion of a GnRH agonist (Ag) and testosterone (T) supplementation on spermatogenesis and the potential fertilizing capacity of sperm in 15 rhesus monkeys. The monkeys were divided into 3 groups of 5 animals each. Groups 1 and 2 received 25 micrograms/day Ag for 44 weeks. Group 2 also received T replacement therapy [sufficient to maintain serum T values within the normal range; 4-5 ng/mL (13.9-17.3 nmol/L)]. Group 3 received a low dose of the Ag (5 micrograms/day for 24 weeks and then 10 micrograms/day for 20 weeks) to prolong the oligospermic phase before the onset of azoospermia. In groups 1 and 3, there was an initial transient (1 week) rise in serum LH and T levels which then fell below pretreatment value where they remained throughout the treatment period. The serum LH and T levels were lower in the group treated with 25 micrograms/day Ag. Similar changes in serum LH levels occurred in group 2, but T supplementation maintained serum T in the physiological range. The decline in serum LH levels was associated with reduced sensitivity to GnRH, since the responses of serum LH and T to GnRH were either abolished or greatly reduced in the 2 groups treated with 25 micrograms/day Ag and were less than 50% of the pre-Ag responses in monkeys treated with 5-10 micrograms/day Ag. Four of five monkeys treated with 25 micrograms/day Ag alone became azoospermic within 21 weeks. All five animals receiving Ag and T supplementation became azoospermic (mean time to onset, 12.6 weeks). Four of five monkeys treated with 5-10 micrograms/day Ag also had azoospermic ejaculates during the late treatment and early recovery period. Sperm counts recovered to the pretreatment levels in most monkeys by 10 weeks of the recovery period. The quality of semen samples taken from oligospermic monkeys was greatly reduced. The percentage of motile and percentage of live sperm per ejaculate, the net negative surface charge on sperm, and the scores of sperm in the hamster oocyte penetration test were subnormal. T supplementation did not improve these measures of semen quality. Testicular biopsies taken at the end of the Ag administration period from monkeys given 25 micrograms/day Ag showed diffuse atrophy of the seminiferous tubules, which contained primarily Sertoli cells and a few spermatogonia and spermatocytes, but no spermatids. The tubular atrophy and the suppression of spermatogenesis did not appear to be influenced by T replacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effect of continuous infusion of a low dose of GnRH antagonist on serum LH and testosterone concentrations, spermatogenesis and semen quality in the rhesus monkey (Macaca mulatta).

Treatment of 4 adult male rhesus monkeys for 8-12 months with 100-400 micrograms of a GnRH antagonist/day by means of using osmotic minipumps led to suppressed serum concentrations of LH and testosterone followed by various degrees of recovery toward pretreatment values. The serum LH response to a challenge of native GnRH was reduced by 30-75% during antagonist treatment. The serum testosterone response to GnRH was exaggerated above the response in the pretreatment period, suggesting hypersensitivity of the testis to gonadotrophin. Antagonist administration under these conditions did not alter body weight or abolish ejaculatory response. Antagonist infusion caused a 96% decrease in sperm counts. Spermatozoa recovered during the final month of antagonist treatment showed a reduced ability to penetrate denuded hamster ova. Testicular biopsies performed at the end of antagonist treatment revealed persistent spermatogenesis. However, the cellularity of the seminiferous tubules was decreased below that of pretreatment biopsies. The results of this study suggest that the amount of testosterone needed to maintain normal spermatogenesis is greater than that needed to maintain electroejaculatory response in monkeys.

Animals↗
PubMed1986

Steroidogenesis by the immature rhesus monkey ovary in vitro.

Primates are believed to have a low level of ovarian steroidogenic activity during prepubertal development. In order to study the rate limiting factors associated with the low level of steroidogenesis, ovaries from prepubertal rhesus monkeys were quartered and incubated for 48 h at 37 C in minimum essential medium. These ovaries secreted 687 +/- 347 pg estradiol/mg ovary and 299 +/- 35 pg progesterone/mg ovary during 48 h of incubation. The addition of 100 ng luteinizing hormone (LH) or 1 mM dibutyryl (Bu)2 cAMP failed to increase significantly estradiol or progesterone secretion. Furthermore, the addition of either progesterone or androstenedione failed to augment estradiol secretion. The presence of either LH or (Bu)2 cAMP with the steroidal substrates also failed to augment estradiol secretion. In contrast, the addition of (Bu)2 cAMP with lipoprotein-derived cholesterol significantly stimulated a two-fold increase in progesterone secretion. The presence of LH in the lipoprotein-supplemented medium failed to augment progesterone secretion. These results suggest that prepubertal monkey ovaries lack the ability to respond to LH, probably due to a lack of gonadotropin receptors or failure of the receptor to stimulate cAMP synthesis. Furthermore, the failure of progesterone and androstenedione to augment estradiol secretion suggests that some cellular components needed to induce aromatase activity are not functional in the prepubertal primate ovary.

Androstenedione↗