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M Ferin

Publications and source records attributed to M Ferin.

At least 37 records · Page 2Linked to original sources
PubMed1996

Interleukin-1 stimulates the central release of corticotropin-releasing hormone in the primate.

The cytokine interleukin-1 (IL-1) is present in the brain and is known to cause a variety of neuroendocrine and immune effects in the rodent; the neuropeptide corticotropin-releasing hormone (CRH) plays a critical role in mediating many of these effects. Little is known about these neuropeptide interactions in the primate. We have therefore examined the effects of IL-1 alpha on the release of CRH in the ovariectomized rhesus monkey in vitro and in vivo. In 3 animals, the effect of IL-1 alpha on CRH release from the superfused hypothalamus was studied in vitro. The hypothalamus was divided in half and fragments from each half were superfused separately. Mean CRH release was 262 +/- (SE) 46 pg/20 min and increased to 1,340 +/- 470 pg/20 min after exposure to IL-1 alpha (p < 0.05). The effect of IL-1 alpha on CRH release into cerebrospinal fluid (CSF) in vivo was studied in 8 animals with chronic cannulas implanted in the lateral ventricle for IL-1 infusion; indwelling catheters were also placed via lumbar puncture and threaded into the cervical area for CSF collection. CSF was collected at a rate of 800 microliters/h during a 4-hour baseline period and for 4-8 h after intracerebroventricular infusion of 4.2 micrograms of IL-1 alpha. CRH increased significantly over time in CSF after IL-1 alpha infusion; the mean concentration of CRH increased from 83 +/- 17 pg/ml during the baseline period to 203 +/- 40 pg/ml after IL-1 alpha infusion (p < 0.01). We conclude that IL-1 stimulates central CRH release in the primate and that the effects of cytokines on the release of this important neuromodulator can be monitored in chronically cannulated animals in vivo.

Animals↗
PubMed1996

The luteinizing hormone but not the cortisol response to arginine vasopressin is prevented by naloxone and a corticotropin-releasing hormone antagonist in the ovariectomized rhesus monkey.

In the primate, arginine vasopressin (AVP) is known to activate the hypothalamo-pituitary-adrenal axis and to inhibit LH secretion. In the present study, we investigate the role of the endogenous opioid peptides and corticotropin-releasing hormone (CRH) in these processes. Adult ovariectomized rhesus monkeys bearing a chronic cannula in the lateral ventricle for intraventricular (i.c.v.) infusion were used. In experiment 1, the effects of 5-hour i.c.v. infusions of saline (n = 7), AVP (50 micrograms/h, n = 7), naloxone (2 mg bolus + 2 mg/h i.v., n = 4) and AVP plus naloxone (n = 4) on LH and cortisol secretion were investigated. As compared to saline and naloxone alone, LH pulse frequency was significantly decreased by AVP (p < 0.05) and by 5 h, the mean LH expressed as a percentage from the 3-hour baseline was also significantly reduced (saline 100.9 +/- 5.1%; naloxone 112.3 +/- 2.9%; AVP 63.3 +/- 8.2%). Coadministration of naloxone abolished the effects of AVP on LH (107.3 +/- 12.1% of baseline). AVP increased cortisol secretion (p < 0.05 vs. baseline), but naloxone did not prevent the increase. In experiment 2, the LH and cortisol responses to AVP were compared in the absence and presence of a CRH antagonist. The antagonist was infused intraventricularly at two doses: 60 and 180 micrograms/h. At both doses, the inhibitory effect of AVP on LH was significantly attenuated (at 4 h, 86.9 +/- 3.2% of baseline; NS vs. saline). However, the CRH antagonist did not block the AVP-induced increase in cortisol. The results confirm previous evidence in the primate of a role of vasopressin in inhibiting the hypothalamo-pituitary-gonadal axis and demonstrate a role of hypothalamic opioid peptides in this process. They also demonstrate that, although CRH is a prerequisite for AVP's action on the hypothalamo-pituitary-gonadal axis, AVP can stimulate the adrenal axis in the primate in the presence of decreased CRH activity.

Adrenal Glands↗
PubMed1996

Interleukin-1 stimulates luteinizing hormone release during the midfollicular phase in the rhesus monkey: a novel way in which stress may influence the menstrual cycle.

We previously demonstrated an inhibitory effect of an inflammatory/immune-like stress challenge, as simulated by intracerebroventricular interleukin-1 alpha (IL-1 alpha) administration, on LH secretion in the ovariectomized rhesus monkey. This was shown to be the result of activation of the hypothalamo-pituitary-adrenal axis by the cytokine. In the present experiments, we have investigated LH and cortisol responses to IL-1 alpha administration in intact monkeys during the follicular phase of the menstrual cycle. Eleven adult rhesus monkeys, bearing an intraventricular cannula for cytokine administration, were used. Cycle parameters were monitored in the preceding control cycles, during the experimental cycles, as well as in subsequent cycles by daily measurements of estradiol and progesterone concentrations and daily menstruation checks. The experiments were performed according to estradiol concentrations: estradiol, 5-38 pg/mL, group 1, early follicular; and estradiol, 50-64 pg/mL, group 2, midfollicular. The effects of intracerebroventricular saline (30 microL/30 min) or IL-1 alpha (4.2 micrograms/30 min) infusions on LH, FSH, and cortisol were compared. After saline infusion, there was no significant change in LH secretion. No significant acute change in LH occurred after IL-1 alpha administration in group 1 (to 0.98 +/- 0.12 ng/mL by 5 h from a baseline of 0.85 +/- 0.12); however, the length of the follicular phase was significantly prolonged in these early follicular phase animals. IL-1 significantly increased LH release in monkeys during the midfollicular phase (group 2; to 2.45 +/- 0.45 ng/mL by 5 h from a baseline of 0.88 +/- 0.11; P < 0.05 vs. baseline and all other groups). FSH was also increased in the latter group. When the experimental observation period was extended to 18 h after IL or saline treatment in eight monkeys, LH and FSH consistently increased after IL administration in three of four animals (to 4.3 +/- 0.7 ng/mL), and in one animal, a surge-like gonadotropin release occurred, whereas no further changes occurred after saline. IL-1 alpha, but not saline, significantly increased cortisol and progesterone release. In conclusion, our results demonstrate that dependent on estradiol concentrations, an acute inflammatory/immune-like stress challenge can affect the hypothalamo-pituitary-ovarian axis differently, either by stimulating gonadotropin release in the presence of significant estradiol concentrations or by inhibiting follicular maturation when given in the presence of low estradiol levels.

Animals↗
PubMed1995

Gonadotropin-releasing hormone neurons in the rhesus macaque are not immunoreactive for the estrogen receptor.

The issue of whether gonadotropin-releasing hormone (GnRH) neurons in the primate contain the estrogen receptor was examined by immunocytochemistry using prepubertal and adult (intact and ovariectomized) female rhesus macaques. No GnRH neurons were found to contain nuclei that were immunoreactive for the estrogen receptor. These results confirm in primates what has been reported in other species and leave open the question of how the effects of gonadal steroids on GnRH neurons are mediated.

Animals↗
PubMed1995

A 5-day estradiol therapy, in amounts reproducing concentrations of the early-mid follicular phase, prevents the activation of the hypothalamo-pituitary-adrenal axis by interleukin-1 alpha in the ovariectomized rhesus monkey.

In a previous report, we have shown that intracerebroventricular (icv) administration of the cytokine interleukin-1 alpha (IL-1 alpha) in the ovariectomized (OVX) rhesus monkey results in the acute activation of the hypothalamo-pituitary-adrenal (HPA) axis and the inhibition of LH and FSH secretion. Here, we compare the cortisol response to IL-1 alpha administration in OVX monkeys and in OVX animals replaced with estradiol (E) to reproduce E concentrations typical of the early-mid follicular phase. Cortisol, LH and FSH were measured after an icv infusion of physiological saline or IL-1 alpha (2.1 or 4.2 micrograms/30 min) in both groups. E-containing capsules were implanted sc 5 days prior to the experiment. In OVX, E concentrations were < 5 pg/ml. Cortisol concentrations decreased throughout the afternoon after saline infusion (to 49.7 +/- 5.1% of baseline at 5 h; n = 7), but increased significantly after IL-1 alpha to 158.3 +/- 13.8% (n = 7). In OVXE, cortisol also declined after saline (to 76.4 +/- 16.2%; n = 5). There were 2 types of response to IL-1 alpha: in grp 1 (mean E: 18.0 +/- 0.7 pg/ml), the cortisol response was similar to that in OVX (160.8 +/- 17.0%; n = 5), while in grp 2 (E: 30.7 +/- 3.1 pg/ml), the cortisol response was absent (66.6 +/- 7.2% of baseline at 5 h; NS vs saline in OVXE; n = 7). The cortisol response to IL-1 alpha was restored in 2 monkeys when E was increased to > 100 pg/ml, confirming our previous observations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1995

Glial ensheathment of GnRH neurons in pubertal female rhesus macaques.

During the period of development, prior to full sexual maturity, gonadotropin hormone-releasing hormone (GnRH) neurons are fully capable of synthesizing and processing the GnRH decapeptide. Nonetheless, the secretion of the hormone is not adequate to stimulate adult patterns of gonadotropin release. The present study was undertaken to examine ultrastructural characteristics of the GnRH neuron and its relationship to its environment in early-midpubertal female rhesus monkey. The neurons bore all the ultrastructural immunocytochemical characteristics of those in mature animals, but quantitative morphometrics revealed that they were extensively apposed by glial processes. Such ensheathment was described earlier in ovariectomized adult animals and was found to be reversible by administration of gonadal steroids. The density of synaptic input to GnRH neurons in the pubertal animals did not differ significantly from that of adult intact or ovariectomized animals from a previous study. Chemical identification will be required to determine whether there are age or hormonal differences in the innervation of these neurons. These results provide anatomical evidence in support of indications from other studies that the ovarian steroidal milieu affects GnRH-glial relationships. Further testing will be required to determine whether the attainment of sexual maturity in the female rhesus macaque is dependent upon a reduction in glial ensheathment of GnRH neurons.

Animals↗
PubMed1995

Effect of chronic opioid antagonism on the hypothalamic-pituitary-ovarian axis in hyperprolactinemic women.

Short term naloxone infusion studies have suggested that enhanced endogenous opioid activity may play a role in inhibiting GnRH and gonadotropin secretion in hyperprolactinemic patients. Because it was not known whether long term opioid antagonism would lead to persistent stimulation of LH with a subsequent ovarian response, we administered the long-acting oral opiate antagonist, naltrexone (NTX), to six hyperprolactinemic amenorrheic women. Blood was drawn from all subjects every 15 min for 10 h on a control day and again on the next day after the administration of 50 mg NTX. Five subjects continued NTX (50 mg daily) for 3-8 weeks. There was a significant increase in the mean concentration of LH (6.7 +/- 1.1 to 12.2 +/- 1.6 IU/L), area under the LH curve (200%), and LH pulse amplitude (3.2 +/- 0.6 to 7.2 +/- 1.0 IU/L) on the first NTX day compared to the control day (P < 0.02). Estradiol levels also increased on the first NTX day (P < 0.01). The mean peak estradiol level increased from 76 +/- 9.9 pmol/L on the control day to 138 +/- 21 pmol/L during NTX treatment (P < 0.02). NTX stimulated LH release in five of six patients, followed by a rise in estradiol in four of these five patients. This initial increase in estradiol was not sustained in most cases, and the mean estradiol level during the entire NTX treatment period was not significantly different from the control level. One patient achieved an estradiol level of 187 pmol/L after 3 weeks of NTX treatment and reported withdrawal bleeding after stopping NTX. No patient ovulated. PRL levels did not change on the first NTX day vs. the control day (166 +/- 79 vs. 167 +/- 67 micrograms/L); however, PRL did increase over time with continued NTX treatment (P < 0.05). The mean PRL level during chronic NTX treatment was 255 +/- 121 micrograms/L. We conclude that treatment of hyperprolactinemic amenorrheic women with NTX results in a prompt partial reactivation of the hypothalamic-pituitary-gonadal axis, as indicated by increased gonadotropin and subsequent estradiol release. The effect of opioid antagonism, however, did not lead to a sustained increase in estradiol secretion with chronic treatment. Thus, although endogenous opioids appear to play a key role in mediating PRL-induced gonadal suppression, chronic opioid antagonism with NTX does not appear to be an effective treatment for amenorrhea in these patients.

Adult↗
PubMed1995

The antireproductive role of corticotropin releasing hormone and interleukin-1 in the female rhesus monkey.

Interleukin-1 alpha (IL-1 alpha) exerts numerous neuroendocrinological and immunological actions. In the ovariectomized (OVX) monkey, intracerebroventricular (icv) infusion of IL-1 alpha stimulates the hypothalamo-pituitary-adrenal (HPA) axis and inhibits pulsatile LH and FSH secretion. This inhibitory effect of IL-1 alpha on the gonadotropins is prevented by coadministration of corticotropin releasing hormone (CRH) and vasopressin (AVP) antagonists, suggesting a role of these two HPA neuropeptides. In order to understand the central mechanisms by which "stress" interrupts the menstrual cycle, we have also investigated the modulatory role of estradiol. When early follicular phase estradiol concentrations are reproduced, there was a complete prevention of HPA activation and of the consequent inhibition of gonadotropin by IL-1 alpha. The mechanisms regulating this unexpected action remain to be elucidated. In contrast, in the presence of late follicular phase estradiol concentrations, the HPA response to IL-1 alpha is restored, but there is a stimulation of LH release. These data demonstrate interactions between the adrenal and gonadal endocrine axes, and highlight the role of estradiol in modulating these effects.

Animals↗
PubMed1994

Inhibitory effect of arginine-vasopressin on LH secretion in the ovariectomized rhesus monkey.

Arginine-vasopressin (AVP) has been previously shown to act in synergism with corticotropin-releasing hormone (CRH) in mediating stress-induced changes in the hypothalamo-pituitary-adrenal (HPA) axis. We have previously shown that both AVP and CRH play a role in mediating IL-1 alpha-induced changes in gonadotropin secretion. In this study, we investigate the effects of exogenously administered AVP on luteinizing hormone (LH) secretion in the ovariectomized (OVX) rhesus monkey. Adult OVX rhesus monkeys were given an intracerebroventricular (ICV) infusion of AVP (15 micrograms/h, n = 8; 50 micrograms/h, n = 5). Control animals received an ICV infusion of physiological saline at a rate 30 microliters/h (n = 12). LH concentrations were measured at 15-min intervals during a 3-hour preinfusion morning baseline and 5-hour postinfusion period. Cortisol concentrations were determined at 45-min intervals. Pulsatile LH release remained unchanged after a control saline infusion. After an AVP infusion, however, LH concentrations (ng/ml) significantly decreased (15 micrograms: from 172.9 +/- 6.4 baseline to 129.4 +/- 5.3; 50 micrograms: from 142.8 +/- 8.3 to 106.7 +/- 6.0, mean +/- SE; p < 0.05). By the fifth hour of the AVP infusion, areas under the LH curve were 64.3 +/- 10.5 and 62.9 +/- 11.0% of morning baseline for 15 and 50 micrograms hourly infusion rate, respectively. While cortisol concentrations decreased throughout the experimental period in the animals receiving saline (a.m.: 35.4 +/- 2.4 micrograms/dl vs. p.m.: 27.7 +/- 1.9 micrograms/dl), they increased after AVP infusion (15 micrograms/h: 42.3 +/- 2.4 vs. 54.6 +/- 2.0 micrograms/dl; 50 micrograms/h: 41.9 +/- 6.6 vs. 50.8 +/- 8.5 micrograms/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

FOS expression in the gonadotropin-releasing hormone (GnRH) neuron does not increase during the ovarian steroid-induced GnRH surge in the rhesus monkey.

The purpose of this study was to investigate the expression of the immediate early gene, c-fos, in GnRH neurons in female rhesus monkeys as a function of generation of the LH surge. Adult monkeys were either intact (n = 6) or ovariectomized (n = 10). Intact animals received estradiol benzoate (EB; 330 micrograms in oil, sc; n = 5) or oil (n = 1). Ovariectomized animals received either EB (n = 5) or EB, followed by progesterone (P; 2.5 ml in oil, im; n = 4), or oil (n = 1). Animals were killed from 31-75 h after EB treatment. Blood samples were collected to document LH release in response to steroid treatment. A surge of LH was initiated in most animals that received EB alone or EB plus P about 30 h after steroid treatment. Animals were perfused with 4% paraformaldehyde, and brain blocks encompassing the region known to contain the majority of GnRH neurons (septum through the medial basal hypothalamus) were cut on the vibratome. Sites of FOS and GnRH immunoreactivities were demonstrated using double labels with a variety of chromogens. Regardless of the time in the surge, there were very few GnRH neurons with FOS immunoreactivity in their nuclei (0-9%). FOS-positive nuclei were seen in many other neurons in various brain regions, including the suprachiasmatic and supraoptic nuclei. There were no differences in FOS expression in GnRH neurons in intact and ovariectomized animals or in steroid- or oil-treated animals. These results suggest that FOS activation in GnRH neurons is not associated with the initiation of the secretory GnRH stimulus to the LH surge in the rhesus monkey. If confirmed, these data suggest that the GnRH nerve terminal may be the primary site for the control of the GnRH surge.

Animals↗
PubMed1994

Stimulatory effects of interleukin-induced activation of the hypothalamo-pituitary-adrenal axis on gonadotropin secretion in ovariectomized monkeys replaced with estradiol.

In a previous report, we have shown that acute activation of the hypothalamo-pituitary-adrenal (HPA) axis by the cytokine interleukin-1 alpha (IL-1 alpha) in the ovariectomized (OVX) rhesus monkey results in an inhibition of LH secretion. Here, we study whether estradiol (E) replacement therapy, at a level that reproduces E concentrations typical of the late follicular phase, modifies the gonadotropin and cortisol responses to IL-1 alpha administration. For E replacement, two Silastic capsules containing E were implanted sc 5 days before the experiment. The serum E concentration increased from less than 5 in OVX to 103.0 +/- 5.2 pg/ml in OVX and E-replaced monkeys. The experimental protocols were carried out 24 h or more after the LH surge that had been induced by E. In Exp 1, the effects of an intracerebroventricular (icv) infusion of physiological saline (group 1) or IL-1 alpha (2.1 or 4.2 micrograms/30 min; group 2) on LH, FSH, and cortisol were compared. IL-1 alpha administration resulted in a progressive release of LH (to 159.0 +/- 8.3% of baseline at 5 h; P < 0.05, 3-5 h vs. saline). Cortisol decreased in group 1 (84.5 +/- 1.3% by 5 h), but increased after IL-1 alpha (147.3 +/- 12.6%; P < 0.05 vs. saline). In Exp 2, we determined whether the stimulatory effects of IL-1 alpha on LH result from the central activation of CRH release (group 3). Infusion of the CRH antagonist, D-Phe12, Nle21,38, CaMe,Leu37-CRF-(12-41) (240 or 360 micrograms/2 h) prevented the increase in LH seen after IL-1 alpha treatment (67.3 +/- 12.5% at 5 h, NS vs. saline). The CRH antagonist also prevented the increase in cortisol and progesterone induced by IL-1 alpha. In Exp 3, we tested whether the stimulatory effect of IL-1 alpha on LH secretion can be simulated by ACTH infusion (group 4). ACTH-(1-24) (10-micrograms bolus plus 50 micrograms/5 h, iv) induced a progressive increase in LH secretion (to 221.5 +/- 27.8% of baseline by 5 h; P < 0.05, 3-5 h vs. saline). ACTH also stimulated cortisol secretion (to 203.3 +/- 30.7% by 5 h). In Exp 4, we investigated the role of adrenal progesterone in the LH response observed in groups 2 and 4. This increase in LH did not occur after pretreatment with RU486, a progesterone antagonist (5 mg Mifepristone; 77 +/- 24.2% by 5 h; P = NS vs. saline), although the increases in cortisol and progesterone were not prevented.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Neuropeptides, the stress response, and the hypothalamo-pituitary-gonadal axis in the female rhesus monkey.

In conclusion, we have demonstrated that in the primate increased activity of the immune system and the consequent IL-1 release result in the activation of neuropeptides of the adrenal axis, mainly CRF and AVP. These neuropeptides, through a direct effect on the GnRH pulse generator or indirectly through the hypothalamic endogenous opioid peptides, inhibit the GnRH pulse generator. Some of the POMC derivatives, such as alpha-MSH, may antagonize these effects. The consequential decrease in GnRH pulse frequency results in an acute decrease in LH and FSH secretion. This decrease in gonadotropin release may explain the deleterious effects of stress on the menstrual cycle. However, an acute decrease in gonadotropins following activation of the adrenal axis is not observed in the presence of estradiol. Thus, during the menstrual cycle, a relative protection against the deleterious effects of acute stress may exist. How potent this protective mechanism is against repetitive stress is not known.

Animals↗
PubMed1992

Alpha-melanocyte-stimulating hormone antagonizes the neuroendocrine effects of corticotropin-releasing factor and interleukin-1 alpha in the primate.

alpha-Melanocyte stimulating hormone (alpha-MSH), a peptide derived from POMC has previously been shown to antagonize the action of exogenously administered beta-endorphin (beta-EP) on pituitary PRL and LH release in the primate. In this study, we have tested the ability of alpha-MSH to block some of the acute pituitary effects of CRF and interleukin-1 alpha (IL-1 alpha), effects which are thought in part to result from the release of endogenous beta-EP. Experiments were performed in ovariectomized rhesus monkeys bearing a chronically implanted lateral ventricular cannula for peptide infusion. Peripheral blood samples for LH, cortisol, and PRL RIA were obtained at 15-min intervals during a 3-h control period when saline was infused into the ventricle, followed by a 5-h experimental period. CRF (15 micrograms/h) infused alone for 5 h caused a significant suppression of pulsatile LH release; by the fifth hour, LH secretion was reduced to 32.5 +/- 2.4% of the control saline infusion. The CRF-induced suppression of LH was prevented by coinfusion of alpha-MSH (60 micrograms/h); by the fifth hour LH was 89.0 +/- 3.6% of the control (P less than 0.05 vs. CRF alone). alpha-MSH also prevented the CRF-induced decrease in LH pulse frequency (P less than 0.05). IL-1 alpha (4.2 micrograms) was infused alone for 30 min or in combination with alpha-MSH (120 micrograms/h for 2 h). After IL-1 alpha alone, LH decreased to 30.1 +/- 2.4% of baseline at 5 h. This decrease was prevented by alpha-MSH; by 5 h LH was 101 +/- 5.1% of baseline (P less than 0.005 vs. IL-1 alpha alone). IL-1 alpha did not affect LH pulse frequency but pulse amplitude was reduced; this reduction was prevented by alpha-MSH (P less than 0.05). IL-1 alpha also stimulated PRL release. PRL rose from a mean baseline of 3.5 +/- 0.3 ng/ml to a peak of 13.8 +/- 2.7 ng/ml; after coinfusion of alpha-MSH the mean peak PRL response was only 4.4 +/- 1.5 ng/ml (P less than 0.001 vs. IL-1 alpha alone). After CRF infusion, cortisol increased to 136 +/- 7.9% of the mean morning baseline concentration. This increase was not prevented by alpha-MSH coinfusion; after CRF plus alpha-MSH, cortisol increased to 121 +/- 6.0% of baseline. In contrast, alpha-MSH prevented the IL-1 alpha-induced increase in cortisol: 167 +/- 15.5% vs. 91.7 +/- 8.3% (P less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Vasopressin mediates the interleukin-1 alpha-induced decrease in luteinizing hormone secretion in the ovariectomized rhesus monkey.

Arginine vasopressin (AVP) has previously been shown to participate in the neuroendocrine control of the adrenal axis. In this study we investigated the role of AVP in the mechanisms linking stress and decreased gonadotropin secretion and evaluated the action of an AVP antagonist on interleukin-1 alpha (IL-1 alpha)-induced changes in gonadotropin and cortisol release in the primate. Adult ovariectomized rhesus monkeys were given a 30-min intracerebroventricular infusion of IL-1 alpha (2.1 micrograms/30 min; n = 5) or IL-1 alpha plus an AVP antagonist (240 micrograms/120 min; [deamino-Pen1,O-Me-Tyr2,Arg8] vasopressin; n = 7); the AVP antagonist infusion was started 30 min before IL-1 alpha and continued for 2 h. Controls included intracerebroventricular infusions of physiological saline (n = 5) or AVP antagonist alone (n = 3). LH concentrations were measured at 15-min intervals during a 3-h preinfusion morning baseline control period and a 5-h postinfusion period. Cortisol concentrations were determined at 45-min intervals. Pulsatile LH release remained unchanged after a control saline or AVP antagonist infusion. Overall LH concentrations decreased significantly after IL-1 alpha infusion, from a morning control baseline of 109.9 +/- 8.8 to 53.7 +/- 3.2 ng/ml after the infusion (P less than 0.05). Concomitant infusion of the AVP antagonist prevented the IL-1 alpha-induced LH inhibition (morning control baseline, 144.5 +/- 6.8; postinfusion, 132.3 +/- 5.8; P = NS vs. saline; P less than 0.0001 vs. IL-1 alpha). While cortisol concentrations decreased throughout the experimental period in the animals receiving saline, they increased after IL-1 alpha infusion: mean +/- SE postinfusion cortisol concentrations were 29.6 +/- 1.9 micrograms/dl (saline) vs. 44.0 +/- 1.7 micrograms/dl (IL-1 alpha; P less than 0.0001). Coinfusion of AVP antagonist and IL-1 alpha did not block the IL-induced cortisol increase (46.8 +/- 1.5 micrograms/dl; P less than 0.0001 vs. morning). After the infusion of AVP antagonist alone, cortisol concentrations significantly decreased from a morning control value of 40.2 +/- 1.6 to 34.9 +/- 1.6 micrograms/dl (P less than 0.05). The results confirm our previous demonstration of an inhibitory effect of IL-1 alpha on gonadotropin secretion in the ovariectomized rhesus monkey and indicate for the first time an important inhibitory role for AVP in the control of gonadotropin secretion during stress. The data also suggest that in this species, the adrenocortical response to IL-1 does not require AVP.

Animals↗
PubMed1992

A surge of gonadotropin-releasing hormone accompanies the estradiol-induced gonadotropin surge in the rhesus monkey.

In several species, the ovulatory LH surge is preceded by a surge of GnRH. Although a role for estradiol in the initiation of the LH surge is well established in the primate, several observations in the rhesus monkey have questioned whether such an estradiol-induced neurosecretory event takes place. We report on GnRH measurements in cerebrospinal fluid (CSF) samples obtained from the third ventricle of intact and ovariectomized (OVX) conscious rhesus monkeys during control periods and throughout the estradiol-induced positive feedback phase. In the first experiment, we measured control GnRH concentrations in CSF collected at 15-min intervals uninterruptedly for a period of 1-5 days in tethered OVX monkeys (n = 4) in their cages without steroid priming. As had been demonstrated previously with the same method in restrained animals, CSF from the third ventricle contained detectable amounts of GnRH. Spontaneous GnRH secretion was pulsatile; overall mean pulse interval was 67.4 (+/- 2.2 SE) min for a total of 177 GnRH pulses. During 2 periods (8 and 6 h) when simultaneous blood and CSF samples were obtained, 14 out of 15 GnRH pulses were accompanied by an LH pulse. To evaluate the effects of an estrogen challenge on GnRH secretion, estradiol benzoate (E2B; 330 micrograms) was given to 4 intact (5 experiments) and to 2 OVX monkeys. CSF collection was initiated 8-24 h before E2B injection and continued for 72-84 h thereafter. E2B administration resulted in a surge of LH and of GnRH in all but one experiment. The mean time of onset of the GnRH surge was 22.0 (+/- 4.0) h after E2B, whereas that of the LH surge was 24.7 (+/- 3.4) h. In contrast to LH, which declined after a peak at 35.2 +/- 3.9 h, the increase in GnRH secretion persisted throughout most of the observation period. The magnitude of the GnRH response differed in the 2 groups; in the intact animals, mean peak GnRH concentration increased 8.9-fold but only 3.8-fold in the OVX monkeys. A similar GnRH surge was observed in 1 OVX monkey, receiving an iv infusion of E2, which produced more physiological concentrations of E2. In this animal, an initial suppression of GnRH concentration in the 24-48 h period after E2 (GnRH control, 14.6 +/- 1.9; post-E2, 4.0 +/- 0.5 pg/ml) preceded the initiation of the GnRH surge which occurred at 54 h after E2.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Modulation of the effects of N-methyl-D,L-aspartate on luteinizing hormone by the ovarian steroids in the adult rhesus monkey.

Although the excitatory amino acid, N-methyl-D,L-aspartate (NMA), is generally thought to stimulate LH release, we have previously reported that NMA inhibits LH secretion in the adult ovariectomized (OVX) rhesus monkey. The objectives of this study were: (1) to compare the effect of NMA on LH in the OVX monkey before and after replacement with ovarian steroids, and (2) to evaluate the LH response to NMA in the intact female monkey during three phases of the menstrual cycle. Three hourly injections of NMA (45 mg i.v.) were given to OVX monkeys (OVX; n = 12) and to OVX animals treated for 4 days with estradiol alone (OVX + E; n = 4) or with estradiol plus progesterone (OVX + E/P; n = 5). Replacement with ovarian steroids prevented the NMA-induced decrease in LH: mean (+/- SE) areas under the LH curve (expressed as a percentage of the 3-hour baseline preinjection control) during the 3-hour NMA treatment period were as follows: OVX, -26.6% +/- 2.4; OVX + E, +69.6% +/- 33.9; OVX + E/P, + 161.5% +/- 59.3 (p less than 0.001 vs. OVX). Three hourly NMA (45 mg i.v.) injections were also given to monkeys in the early to mid-follicular phase (n = 5), the late follicular phase (n = 6) and the luteal phase (n = 11). NMA significantly increased LH in the luteal phase: control, 11.5 +/- 2.1; peak LH response, 19.8 +/- 2.1 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

An inhibitory effects of interleukin-1a on basal gonadotropin release in the ovariectomized rhesus monkey: reversal by a corticotropin-releasing factor antagonist.

Interleukin-1 (IL-1), an important component of the immune system, has recently been shown to influence the release of several hormones in the rodent. In this paper, the effectiveness of IL-1a in modulating basal gonadotropin secretion as well as cortisol release in the primate has been investigated. Eight adult ovariectomized rhesus monkeys were given a 30-min intracerebroventricular infusion of physiological saline (n = 5), various doses of IL-1a (17 micrograms n = 5; 8.5 micrograms; n = 3; 4.2 micrograms n = 5; and 2.1 micrograms n = 4) or IL-1a plus a CRF antagonist (n = 5). LH and FSH concentrations were measured at 15-min intervals during the 3-h preinfusion baseline control and the 5-h postinfusion period, while cortisol concentrations were determined at 45-min intervals. While LH concentrations remained unchanged in the monkeys receiving saline only, they decreased significantly after the 30-min IL-1a infusion. By hour 5 after IL-1a administration, mean (+/- SE) hourly areas under the LH curves (expressed as a percentage of preinfusion baseline) were 27.7% +/- 7.3 (17 micrograms IL-1a), 31.9% +/- 8.4 (8.5 micrograms), 33.3% +/- 5.5 (4.2 micrograms), and 39% +/- 4.0 (2.1 micrograms) (P less than 0.05 vs. morning control). FSH concentrations were also significantly decreased after IL-1a, 17 micrograms: by hour 5, they were 67.4% +/- 5.0 of baseline control. While cortisol concentrations decreased thoughout the experiment in the animals receiving saline, they increased with all IL-1a doses: overall mean (+/- SE) postinfusion concentrations were 21.8 +/- 1.1 (saline), 49.5 +/- 2.2 (IL-1a, 17 micrograms), 35.1 +/- 1.9 (8.5 micrograms), 45.7 +/- 1.5 (4.2 micrograms), and 39.5 +/- 1.5 (2.1 micrograms) micrograms/dl (P less than 0.05 IL-1a vs. saline). Concomitant infusion of the CRF antagonist, [D-Phe12, NLE 21,38caMe LEU37] CRF (12-41), (120-360 micrograms), prevented the IL-1a induced LH inhibition. By hour 5, areas under LH curves were 33.5% +/- 1.7 for IL-1a alone and 99.2% +/- 4.2 (NS vs. saline) for IL-1a + CRF antagonist. The CRF antagonist also blocked the ability of IL-1a to increase cortisol secretion: mean cortisol concentrations were 28.6 +/- 1.4 micrograms/dl (NS vs. saline). The results clearly indicate that the cytokine IL-1a inhibits pulsatile LH and FSH secretion in the ovariectomized rhesus monkey and demonstrate that this inhibition is causally related to the activation of CRF by this cytokine.(ABSTRACT TRUNCATED AT 400 WORDS)

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