Biomedical subjects

D L Hess

Publications and source records attributed to D L Hess.

At least 73 records · Page 4Linked to original sources

PubMed1993

Chlamydia in the neonate.

Chlamydia trachomatis infections are the most prevalent of all sexually transmitted diseases and can be transmitted to the neonate during the birth process. Neonatal chlamydial infections include inclusion conjunctivitis and chlamydial pneumonia. These infections cause no reported mortality but are associated with a high incidence of morbidity in the newborn. Nursing care is vitally important in prevention, early detection, and management of neonates with chlamydial infections. A knowledge of Chlamydia, its risk factors, clinical manifestations, diagnosis, and treatment will assure an improved outcome for the entire neonatal population.

Chlamydia Infections↗

PubMed1992

Sex differences in adrenal function in the lizard Cnemidophorus sexlineatus: I. Seasonal variation in the field.

In order to document sex differences in adrenal function and how this relates to gonadal function during the period of seasonal activity, blood samples from male and female six-lined racerunners, Cnemidophorus sexlineatus, were taken immediately after capture in the field for determination of plasma corticosterone and gonadal steroid concentrations. Plasma testosterone and dihydrotestosterone levels for males, and 17 beta-estradiol and progesterone levels for females, were measured. Trends in the concentration of plasma corticosterone differed significantly between males and females. In males the highest concentrations of corticosterone were measured in late spring and the lowest concentrations were measured in late summer. Whereas half of the variation in corticosterone levels among males could be explained as seasonal change, less than 1% of the variation among females could be explained as seasonal change. In males plasma corticosterone and androgens exhibited similar seasonal decreases. Corticosterone levels for females were not correlated with progesterone or 17 beta-estradiol levels. Sex differences in seasonal variation in plasma corticosterone concentrations suggest that corticosterone may be involved in the different reproductive strategies and energy requirements of males and females during the seasonal period of activity.

Adrenal Glands↗

PubMed1992

Sex differences in adrenal function in the lizard Cnemidophorus sexlineatus: II. Responses to acute stress in the laboratory.

Circulating concentrations of plasma corticosterone and gonadal steroids were measured in intact and gonadectomized male and female lizards (Cnemidophorus sexlineatus) following acute stress (handling) in the laboratory. There was a significant increase in plasma corticosterone after stress. Whereas intact females exhibited greater concentrations of corticosterone relative to intact males, ovariectomized females exhibited lower concentrations of corticosterone relative to castrated males. In addition to sex differences in corticosterone responses to gonadectomy, progesterone was elevated by stress in both intact and ovariectomized females but not in males. Corticosterone adjusted for castration and handling in males was negatively correlated with the plasma androgen level. The adrenal responsiveness of males to acute stress may be attenuated by androgens presumably secreted by the testis. Not only does adrenal function influence reproduction, but adrenal responses differ between males and females, and appear to be influenced by the gonadal axis. The sex differences in adrenal responses to stress likely reflect different reproductive strategies and nutritional requirements of males and females during the breeding season.

Adrenal Glands↗

PubMed1992

Embryotoxicity studies of norfloxacin in cynomolgus monkeys. II. Role of progesterone.

Norfloxacin, an orally active fluoroquinolone antimicrobial, has been reported to be embryolethal but not teratogenic when administered to pregnant cynomolgus macaques prior to gestational day (GD) 36 at doses > or = 200 mg/kg/day. Additional studies have been performed in an effort to examine the mechanism responsible for this effect, particularly regarding the role of progesterone (P). The first study (Study I) investigated the effect of norfloxacin administration during early pregnancy (200 mg/kg/day; daily GD 20-30) in the absence of a functional corpus luteum (CL). The CL was surgically removed from 16 gravid females on GD 19 in order to focus on placental-derived P; ten were dosed with norfloxacin and six received vehicle only. Embryolethality was observed for 7/10 (70%) of the treated animals during GD 25-31 versus 0/6 (0%) for controls. A reduction in serum P was noted prior to embryonic loss, although no significant effects on chorionic gonadotropin (CG), 17 beta-estradiol (E2), or P or E urinary metabolites were observed. A second study (Study II) was performed in order to evaluate the capacity of norfloxacin (200 mg/kg) to reduce CL-derived P in both normally cycling and CG-stimulated nonpregnant females (ten treated, ten controls; daily for 8 days). No effects on P production or on luteal phase or menstrual cycle lengths were observed. The third study (Study III) was designed to examine the effect of norfloxacin on the metabolism and excretion of P in nonpregnant females. Silastic P implants were placed subcutaneously in order to maintain constant P levels during a 10 day treatment regimen (200 mg/kg/day; ten controls, nine treated). Five of the controls and four of the norfloxacin-treated females also received 14C-P intravenously within 1 hr of the last dose of norfloxacin in order to study excretory patterns. No significant differences between control and treated groups were observed. The results of these studies combined suggest that the developmental toxic effects observed in prior studies and Study I are specific to pregnancy and directly related to placental-derived P production.

Animals↗

PubMed1992

Influence of corpus luteum age on the steroidogenic response to exogenous human chorionic gonadotropin in normal cycling women.

OBJECTIVE: The null hypothesis of this study is that the patterns of steroid secretion exhibited by the human corpus luteum in response to exogenous human chorionic gonadotropin stimulation are independent of corpus luteum age at the time of treatment. STUDY DESIGN: Twenty-five normally cycling women in whom the midcycle urinary luteinizing hormone surge (luteal day 0) was identified and from whom blood samples were obtained daily from cycle day 11 until menses were prospectively randomized to receive no treatment (group I, n = 5) or exogenous human chorionic gonadotropin 5000 IU administered intramuscularly on luteal day 0 (group II, n = 5), +4 (group III, n = 5), +8 (group IV, n = 5), or +12 (group V, n = 5). Serum concentrations of estrone, estradiol, progesterone, 17-hydroxyprogesterone, and androstenedione were measured by specific radioimmunoassays in all subjects; serum human chorionic gonadotropin concentrations were determined by immunoradiometric assay in treated subjects. RESULTS: Serum human chorionic gonadotropin levels (mean +/- SEM) were virtually identical among treatment groups (p greater than 0.05). Luteal phase duration (mean +/- SEM) was prolonged (p less than 0.05) only in group V (18.4 +/- 0.5 days) compared with untreated subjects (group I 13.8 +/- 0.7 days). In all groups estrone and 17-hydroxyprogesterone concentrations closely paralleled those of estradiol and progesterone, respectively. Steroid data and progesterone/estradiol ratios (mean +/- SEM) in groups I and II were indistinguishable and were combined (control, n = 10). Group III subjects exhibited patterns of steroid secretion similar to groups I and II, although progesterone was moderately increased after human chorionic gonadotropin treatment. In groups IV and V, progesterone increased (p less than 0.05) 1 day after human chorionic gonadotropin and remained elevated for 5 to 6 days; a 4-day rise (p less than 0.05) in estradiol began 3 days after treatment, and androstenedione rose modestly in parallel. Progesterone/estradiol ratios in groups III through V increased (p less than 0.05) approximately twofold after human chorionic gonadotropin treatment and remained elevated for 4 to 5 days. CONCLUSION: The human corpus luteum exhibits distinct age-dependent patterns of steroid secretion in response to exogenous human chorionic gonadotropin stimulation, an observation that may have clinical implications regarding the empirical use of exogenous human chorionic gonadotropin in support of luteal function.

Adult↗

PubMed1992

Excessive testicular progesterone secretion in aged male Fischer 344 rats: a potential cause of age-related gonadotropin suppression and confounding variable in aging studies.

Previous studies have inconsistently reported elevated sex steroid levels in aging male F344 rats, which frequently develop testicular Leydig cell tumors. The aims of this study were to characterize circulating steroid levels and to determine the in vivo source and functional significance of altered steroid secretion in these animals. Progesterone (P) and to a lesser extent estradiol (E2) levels were increased, while gonadotropins and testosterone (T) were decreased, in intact 24-mo-old compared to 12-mo-old rats. P levels were inversely correlated with gonadotropins and T. All old rats demonstrated Leydig cell hyperplasia or tumors. After orchidectomy, P levels were markedly decreased. Gonadotropin levels were similar in orchidectomized 24-mo compared to 3-mo-old rats. We conclude that the testis is the source of excessive P and E2 secretion in vivo in old F344 rats. Increased P (or E2) negative feedback may contribute to the suppression of gonadotropins and reproductive function in aging male F344 rats. Finally, excessive P secretion may be a confounding pathological variable in aging studies using this rat model.

17-alpha-Hydroxyprogesterone↗

PubMed1992

The Sulawesi Crested Black Macaque (Macaca nigra) menstrual cycle: changes in perineal tumescence and serum estradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone levels.

Events in the normal menstrual cycle of the endangered Sulawesi Crested Black Macaque (Macaca nigra) were characterized. Daily blood samples were obtained during 10 menstrual cycles from five M. nigra demonstrating regular cycles. The amount of perineal tumescence was scored daily. Serum levels of estradiol and progesterone were determined by RIA, serum LH levels were determined by the mouse Leydig cell bioassay, and serum FSH levels were determined by the rat granulosa cell aromatase bioassay. Cycle length was 39.8 +/- 1.0 days (mean +/- SEM) with an LH surge occurring 25 +/- 1.5 days from the onset of menses. After menses, both LH and estradiol were initially depressed, with estradiol first exceeding 50 pg/ml 8 days before the LH surge. In five cycles, peak estradiol levels (340 +/- 44 pg/ml) occurred on the day of the LH surge (637 +/- 58 ng/ml) and in the other five cycles, on the day before the LH surge. There was a broad increase of FSH in midcycle without a well-defined surge corresponding to the LH surge. Progesterone began increasing on the day of the LH surge and reached peak levels (6.8 +/- 0.96 ng/ml) 8 days later. Maximal perineal tumescence was generally associated with the time of the LH surge, but variation between animals made it impossible to predict accurately the day of the LH surge by perineal tumescence scores alone.

Animals↗

PubMed1991

Circadian myometrial and endocrine rhythms in the pregnant rhesus macaque: effects of constant light and timed melatonin infusion.

Six chronically catheterized rhesus macaques maintained on a 12-hour-light/dark cycle (lights on from 7 AM to 7 PM) showed a nocturnal uterine activity rhythm with peak contractile events between 9 and 11 PM (p less than 0.05). In blood samples collected at 3-hour intervals over a 24-hour period, we determined that plasma melatonin and progesterone concentrations were elevated at night whereas estradiol, estrone, and cortisol reached peak concentrations in the early morning (p less than 0.05). Lights were then left on for the remainder of the study. After 12 days in constant light, daily rhythms in uterine activity and plasma steroid levels were relatively unchanged, whereas melatonin concentrations were suppressed. Animals then received a timed infusion of melatonin (0.2 mg/kg/hr each day from 7 PM to 6 AM daily until delivery). The nocturnal uterine activity rhythm and the rhythms in plasma steroid concentrations were maintained. We conclude that the 24-hour patterns in maternal uterine activity and plasma steroid hormone levels are circadian rhythms generated by an endogenous biologic clock and do not appear to be driven by the pattern of melatonin in circulation.

Animals↗

PubMed1991

Reproductive hormone levels after pituitary allograft in cyclosporin-treated monkeys.

OBJECTIVE: To determine the course of events during the onset of hyperprolactinemic amenorrhea, a nonhuman primate model was sought that did not require suckling or interference with the in situ hypothalamic-pituitary axis. DESIGN: Because removal of the adenohypophysis from hypothalamic influence results in secretion of large quantities of prolactin (PRL) but little of the other adenohypophyseal hormones, we explored the possibility of establishing pituitary allografts in monkeys. Normally cycling female rhesus monkeys were immunosuppressed with a daily regimen of cyclosporin A (CyA; 10 to 15 mg/kg per day) and then subcutaneously grafted with a pituitary from another animal (allograft). Blood samples were obtained daily via saphenous vein puncture during control, only CyA-treatment, and allografted-plus CyA- menstrual cycles. SETTING: Oregon Regional Primate Research Center, Beaverton, Oregon. PARTICIPANTS: Female Macaca mulatta exhibiting regular menstruation. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prolactin, luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels were determined in harvested serum. RESULTS: Temporary survival of 5 of 11 (45%) allografts was assumed based on elevations in serum PRL. Of the viable grafts, 4 of 5 (80%) resulted in reproductive dysfunction, as first evidenced by delay or loss of the preovulatory rise in E2. When the peak of follicular E2 was delayed, then the LH surge occurred, but it was also delayed. If follicular E2 levels did not peak, then the LH surge was absent as was luteal P production. CONCLUSION: These data suggest that in the etiology of PRL-induced infertility in women, the first event is a suppression of follicular E2 production. In addition, the hypothalamus probably remains responsive to the positive feedback of E2 during early or moderate hyperprolactinemia.

Animals↗

PubMed1991

Effects of neuropeptide Y on the in vitro release of gonadotropin-releasing hormone, luteinizing hormone, and beta-endorphin and pituitary responsiveness to gonadotropin-releasing hormone in female macaques.

The objectives of these studies were to examine the release of gonadotropin-releasing hormone (GnRH) and beta-endorphin-like activity (beta-EP) from macaque hypothalami, and the release of luteinizing hormone (LH) and GnRH-induced LH from macaque anterior pituitaries in response to neuropeptide Y (NPY) treatment. Anterior hypothalamic (AH) and mediobasal hypothalamic (MBH) blocks of tissues and the adenohypophysis were bisected along the midline into two equal-sized fragments. Fragments were superfused with medium for 3 h, followed by 3 h of either NPY (80 nM) or medium alone. In a separate experiment, adenohypophyseal (AP) fragments were superfused in accordance with the same protocol (3 h medium - 3 h NPY or medium) except that exogenous GnRH (352 nM) was added for 30 min at the beginning of hour 3 and again at the beginning of hour 6. Immunoactive GnRH, beta-EP, and LH levels were measured in superfusate samples (400 microliters) collected at 10-min intervals. GnRH levels rose within 20-30 min of initiation of NPY treatment, and elevated GnRH release was sustained for the duration of NPY exposure of both AH and MBH fragments from ovarian intact (INT) rhesus (Macaca mulatta: n = 8; p less than 0.05) or Japanese (Macaca fascicularis; n = 4; p less than 0.01) macaques. NPY treatment had no effect on either AH or MBH fragments isolated from ovariectomized (OVX) rhesus macaques (n = 4 for AH, and n = 5 for MBH). In AP fragments isolated from INT rhesus macaques (n = 8), NPY stimulated LH release within 1 h of treatment (p less than 0.05), whereas NPY had no effect on pituitaries from OVX animals (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Endocrine and morphological maturation of the fetal and neonatal adrenal cortex in baboons.

Developmental changes in basal and circadian fluctuations in plasma dehydroepiandrosterone sulfate (DHEAS) and cortisol (F) from birth until 3 months of life were studied in conjunction with morphological characteristics of the fetal and neonatal adrenal cortex in baboons (Papio anubis). These studies were complimented by measurements of in vitro production of DHEAS and F (basal and ACTH stimulated) by adrenal tissue slices. Cortisol, DHEAS, estrone, estradiol, and progesterone were determined in plasma and incubation medium by specific RIA. After delivery, an initial rise in plasma DHEAS was sustained for 4 days, followed by a precipitous decline, which reached a nadir between days 10-12 postpartum. Thereafter, plasma DHEAS and F concentrations stabilized with minor fluctuations. A significant (P less than 0.05) and persistent diurnal rhythm in DHEAS and F secretion was evident by the end of the first week after birth. Administration of estrone acetate and progesterone in oil maintained neonatal plasma concentrations of estrone, estradiol, and progesterone at levels comparable to those in utero, but had no quantitative or qualitative effect on the pattern of plasma DHEAS or F in the neonate. The relative production of F to DHEAS by tissue slices in vitro (the calculated F/DHEAS ratios) indicates that DHEAS secretion by the fetal adrenal is 10-fold higher than that of F near parturition; ACTH stimulation does not alter this relationship. By postnatal day 10, the basal production rates of F and DHEAS are equivalent, and the response to ACTH stimulation favors production of F. With advancing neonatal age (at 30 and 100 days), there is an increase in the F/DHEAS secretion ratio both during the basal state and in response to ACTH. The baboon adrenal glands increased in weight during the last month of gestation and then stabilized during the early postnatal period; a gradual increase in weight was observed after 30 days postpartum. Within 2 weeks after parturition, the relative width of the fetal zone decreased dramatically to occupy less than one third of the total cortex. During involution, we observed a decrease in cell size and a reduction in cytoplasmic vacuolation. A zone of closely packed cells with numerous areas of cell death (the dense band) separated the zona fasciculata from the fetal zone. Cell proliferation was observed in the upper regions of the definitive cortex. We conclude the following. 1) The hypothalamic-hypophyseal mechanisms that regulate the diurnal adrenal secretory rhythm are established in the early neonatal period in the baboon.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗

PubMed1991

Comparison of plasma oxytocin and catecholamine concentrations with uterine activity in pregnant rhesus monkeys.

Pregnant rhesus monkeys exhibit diurnal changes in uterine activity (UA), with episodes of increased UA during the early hours of darkness. The estrogenic environment during late pregnancy serves a permissive role in the maintenance of nocturnal UA episodes and may involve myometrial interactions with oxytocin (OT) and/or alpha-adrenergic stimuli. In the present study we have used chronically catheterized pregnant rhesus monkeys to measure diurnal changes in maternal plasma OT, epinephrine, norepinephrine, and dopamine. We also determined the effects of infusing an OT antagonist (ORF 22164) and the alpha-adrenergic antagonist phentolamine on nocturnal UA episodes. Animals were exposed to a 16-h light, 8-h dark photo-period, with the hours of darkness between 2300-0700 h. Maternal plasma samples were collected at 3-h intervals for 36 h and analyzed by RIA for OT and by high performance liquid chromatography for catecholamines. Plasma OT was correlated with UA in animals that displayed nocturnal UA episodes (r = 0.76; P less than 0.01). Maximal OT concentrations occurred at 2400 h in these animals; plasma OT was higher during the hours of darkness compared to levels during the light phase (10.4 +/- 1.9 and 3.0 +/- 0.3 pmol/L, respectively; n = 4). Some animals did not display nocturnal episodes of increased UA and showed no increase in OT concentrations during the hours of darkness. Maternal plasma catecholamine concentrations were not correlated with nocturnal UA and were maximal during the light phase. Nocturnal UA was abolished within 30 min of infusion of the OT antagonist, but phentolamine infusions had no effect on nocturnal UA. We conclude that 1) changes in maternal plasma catecholamine concentrations are not involved in the generation of nocturnal UA; 2) the presence of episodes of increased UA at night results from increased maternal plasma OT concentrations; and 3) the absence of nocturnal UA in some animals can be explained by a reduced level of OT secretion.

Animals↗

PubMed1990

Acute administration of estrogen suppresses LH secretion without altering GnRH release in ovariectomized rhesus macaques.

The pattern of hypothalamic gonadotropin-releasing hormone (GnRH) release was examined during estrogen (E)-induced suppression of plasma luteinizing hormone (LH) in ovariectomized (OVX) rhesus macaques. In Expt. 1, 4 OVX macaques were fitted with a jugular catheter and a push-pull cannula (PPC) directed into the median eminence (ME). Push-pull perfusion (PPP) was initiated 10 h before and continued for 10 h after subcutaneous estradiol benzoate (EB) injection (42 micrograms/kg b.wt.). In Expt. 2, 4 additional monkeys were subjected to local intrahypothalamic perfusion with estradiol-17 beta (E2, 3 microM) for the last 10 h of a 20-h PPP. In Expt. 2, OVX animals were challenged with 5 micrograms exogenous GnRH 3 h before and 8 h after EB injection to test for changes in altered LH release. Integrated 10-min ME perfusate and intermittent 10- or 60-min peripheral plasma samples were assayed for GnRH and LH by radioimmunoassay and bioassay, respectively. In addition, 2 other OVX macaques that received similar ME-PPC placement were sacrificed 2 days after the completion of a PPP for immunocytochemical labeling of GnRH neurons at the perfusion site. The results show that after EB, hypothalamic GnRH (MBH-GnRH) release remained unaltered while LH levels declined rapidly (Expt. 1). Similarly, intrahypothalamic perfusion of E2 failed to change the pattern of MBH-GnRH release in any of 4 monkeys (Expt. 2). Conversely, plasma LH release in response to exogenous GnRH was greatly reduced after EB (Expt. 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Germinal cell ectopism in the strepsirhine prosimian Galago crassicaudatus crassicaudatus.

The presence of germinal cells outside of the embryonal and fetal gonads of the strepsirhine prosimian Galago crassicaudatus crassicaudatus is described. Forty-three embryos and fetuses from day 26 or 27 of gestational age to near term were studied: more than 90% possessed germinal cells in ectopic sites situated either far from (extragonadal ectopism) or close to the gonads (perigonadal ectopism). The first sites were the walls of the aorta and mesenteric artery, the stroma between the aorta and the cardinal vein, and the retroperitoneal neuroganglia. The second were the mesenchyme dorsal to the gonads and around the vestigia of the mesonephric glomeruli and tubules, and the rete ovarii and testis. The ectopic cells were generally present in conscpicuous numbers, in some animals being more numerous than in the gonads. Those situated far from the gonads underwent degeneration and decreased significantly in numbers during post-embryonal stages of development, while the others remained numerous and functionally active up to near term. While the differentiation of the extragonadal germinal cells after day 60 of gestational age could not be studied due to technical difficulties, the XX and XY cells in perigonadal sites appeared to follow patterns of differentiation identical to those of their entopic counterparts.

Animals↗

PubMed1990

Gonadotropin-releasing hormone and norepinephrine release from the rabbit mediobasal and anterior hypothalamus during the mating-induced luteinizing hormone surge.

The release of hypothalamic GnRH in association with the mating-induced LH surge was studied in the rabbit. Push-pull perfusion (PPP) of the mediobasal (MBH) or anterior (AH) regions of the hypothalamus was performed on conscious, unrestrained does for 3 h before and 5 h after exposure to a vasectomized buck. In experiment 1, GnRH concentrations were measured by RIA in 20-min fractions of MBH-PPP. An approximately 100-fold increase in GnRH release was observed within 1 h of coitus (pre, 1.15 +/- 0.29 pg/ml; peak, 106.67 +/- 37.42 pg/ml; n = 6; P less than 0.05). Concomitant surges of LH and PRL in the peripheral circulation were observed. In experiment 2, GnRH and norepinephrine (NE) were measured (the latter by radioenzymatic assay) in 10-min fractions of MBH-PPP. A 218% postcoital rise in NE levels (n = 5; P less than 0.05) in MBH-PPP accompanied an approximately 50-fold peak rise in GnRH in the same samples (pre, 1.57 +/- 0.23 pg/ml; peak, 76.52 +/- 50.14 pg/ml; P less than 0.05). MBH-NE, MBH-GnRH, LH, and PRL release began rising within 10 min of coitus. In experiment 3, GnRH was measured in 20 min fractions of AH-PPP. Coitus induced a marked rise in AH-GnRH release (precoitus, 0.31 +/- 0.03 pg/ml; peak, 2.25 +/- 0.80 pg/ml; n = 4; P less than 0.05) which differed from coitus-induced MBH-GnRH release both quantitatively (i.e. approximately 7-fold increase for AH vs. approximately 50-100-fold increase for MBH; 50-min lag time for AH vs. less than 20 min for MBH) and qualitatively (i.e. AH-GnRH release was discontinuous, while MBH-GnRH release rose sharply, plateaued, and then declined slowly over the 2-5 h following coitus). No changes in MBH-NE, MBH-GnRH, AH-GnRH, LH, FSH, or PRL were observed in sham-mated does (Exp 1, n = 7; Exp 2, n = 3; Exp 3, n = 4). These data support the hypotheses that: 1) hypothalamic GnRH release is a component of reflexive ovulation in the rabbit; 2) increased hypothalamic noradrenergic tone is related to the surge-release of GnRH; and 3) AH-GnRH release is enhanced following coitus.

Animals↗

PubMed1990

Third-ventricular infusion of neuropeptide Y suppresses luteinizing hormone secretion in ovariectomized rhesus macaques.

Neuropeptide Y (NPY) has been shown to modulate gonadotropin secretion in an estrogen-dependent manner in the rat and rabbit, and to act centrally in these species to alter GnRH release. The present study examined the ability of centrally administered NPY to affect LH secretion in the primate. Human NPY (hNPY) was administered into the third cerebroventricle of unanesthetized, freely moving, ovariectomized (OVX), or estradiol (E2)-treated OVX rhesus monkeys. LH was measured in blood samples collected remotely at 10-min intervals throughout the experiments. An extensive range of NPY doses was tested in a preliminary study in which OVX monkeys received a 3-h control infusion of Krebs Ringer phosphate buffer (KRP) followed immediately by a 3-h infusion of hNPY (0.1-50 micrograms/h). Only doses greater than or equal to 5 micrograms/h produced a consistent and marked suppression of LH (5 micrograms/h; 35.1 +/- 7.2% reduction, P less than 0.05, n = 4). A longer duration study was performed to better characterize changes in LH pulse frequency and amplitude produced by hNPY treatment. We administered 5 micrograms/h and 15 micrograms/h to OVX (n = 5) and E2-treated OVX (n = 4) monkeys according to the following protocol: 8 h control KRP/8-h hNPY/6-h recovery KRP. In OVX monkeys, LH was suppressed after 2 to 3 h of peptide infusion (P less than 0.01); LH secretion returned to normal after treatment. Both doses of hNPY suppressed mean LH by approximately 55% (P less than 0.05) and LH pulse frequency by approximately 69% (P less than 0.025). LH pulse amplitude was unaffected. In E2-treated OVX monkeys, neither dose of hNPY affected mean LH or LH pulse amplitude. LH pulse frequency was suppressed by approximately 65% (P less than 0.05) during 15-micrograms/h treatment. Because centrally administered hNPY reduced LH pulse frequency and thereby mean LH levels, our results support a central, neural action of NPY to affect the GnRH/LH secretory system. The ability of estrogen feedback to alter the response to NPY treatment supports a physiological role for NPY in controlling reproduction in the primate.

Animals↗

PubMed1989

Embryotoxicity studies of norfloxacin in cynomolgus monkeys: I. Teratology studies and norfloxacin plasma concentration in pregnant and nonpregnant monkeys.

Norfloxacin, a new orally active antibiotic, was investigated in cynomolgus monkeys for potential developmental toxicity. Fifty-seven monkeys were administered a control vehicle or norfloxacin by nasogastric gavage during the major period of organogenesis on gestational days (GD) 21 through 50 at doses of 0, 50, 100, 150, or 200/300 mg/kg/day. There was no evidence of teratogenicity at any dose level. Maternotoxicity and a significant increase in embryolethality occurred following doses of 200/300 mg/kg/day. The maternotoxicity was not expected based on range-finding studies in nonpregnant female monkeys, which showed no signs of toxicity in doses up to 500 mg/kg/day. Additional studies were conducted to determine if norfloxacin caused similar toxicity later in gestation. Forty-six pregnant monkeys were dosed with a control vehicle or 200 mg/kg/day norfloxacin for one of three 10-day periods on GD 36-45, 71-80, or 111-120. There were no maternotoxic, embryotoxic, or fetotoxic effects observed. Plasma concentrations of norfloxacin in five cynomolgus monkeys following 50 and 200 mg/kg oral doses were not dose-proportionate. However, at a given dose, administered in cross-over fashion, plasma concentrations of norfloxacin were higher in nonpregnant females (approximately 20-40%) than during pregnancy when the same subject was compared. At the no-observed-effect dose for maternal and embryotoxicity (50 mg/kg), peak plasma concentrations of norfloxacin in pregnant cynomolgus monkeys are approximately threefold higher than those observed in human volunteers receiving norfloxacin at the maximum recommended therapeutic dose of 400 mg (5.7 mg/kg based on 70 kg body weight) twice per day.

Animals↗

PubMed1989

In vitro fertilization and embryo transfer in the rhesus monkey.

Twenty-three rhesus monkeys were subjected to 9 days of ovarian hyperstimulation with sequential exposure to human follicle-stimulating hormone (hFSH) and then human luteinizing hormone (hLH) + hFSH. Six animals (26%) did not exhibit sustained, elevated levels of circulating estradiol, primarily due to the occurrence of a premature surge of endogenous LH (n = 4). Seventeen animals (74%) responded with supraphysiologic levels of circulating estradiol (peak value: means = 4480 pg/ml) and received human chorionic gonadotropin (hCG) on Day 10. Oocytes were collected 26 h later by aspiration of large antral follicles. Oocyte quantity (means = 18/animal) and quality (63% mature) were evaluated by in vitro fertilization (IVF), embryonic development, and embryo transfer to foster mothers. Modified conditions for the successful fertilization of oocytes used a Tyrode's augmented (TALP) medium supplemented with 0.3% bovine serum albumin (BSA). Oocytes were inseminated at the metaphase II stage with ejaculated, washed sperm (50 100 x 10(3)/ml) preexposed at ambient temperature to caffeine and dibutyryl cyclic adenosine 3'5'-monophosphate. Successful fertilization ranged from 26% to 75%. In one experiment, 5 of 11 embryos produced by IVF developed in vitro to hatched blastocysts. Embryo freezing employed a propanediol-based protocol and was applied to early cleavage-stage embryos with 100% (5 of 5) post-thaw survival. Two frozen-thawed embryos were transferred transtubally on 3 occasions into rhesus monkeys during the early luteal phase of spontaneous menstrual cycles. One pregnancy resulted, which proceeded normally to the unassisted delivery of a male offspring 170 days after the LH surge. We conclude that this sequential regimen of human gonadotropins provides a cohort of oocytes from rhesus monkeys that will complete meiotic maturation and fertilize in vitro, with embryonic development proceeding in vitro and in vivo. The production of putative antibodies to human gonadotropins, assessed by the presence of Protein A-precipitated hCG binding components in sera, limits the repeated use of monkeys in the hyperstimulation protocol. Nevertheless, this model system should facilitate further studies on oocyte maturation, fertilization, and early embryogenesis in primates.

Animals↗