Biomedical subjects
Publications and source records attributed to J S Kesner.
The increase in serum cortisol concentrations following naloxone administration to female pigs was abolished by hypophysial stalk-transection, even though CRH and ACTH stimulated cortisol release in these animals. We suggest that the opioid antagonist enhances cortisol secretion primarily by a central action in pigs.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In the rhesus monkey (Macaca mulatta), the frequency of pulsatile gonadotropic hormone release is relatively constant in the face of widely varying levels of estradiol (E2) in the peripheral circulation--e.g., in the course of the follicular phase of the menstrual cycle and after ovariectomy. This suggests that modulation of the hypothalamic gonadotropin-releasing hormone (GnRH) "pulse generator" by this steroid is not of major physiological importance. Herein is described the unexpected inhibition or total blockade of the electrical activity of this pulse generator in ovariectomized monkeys by physiological levels of exogenous E2. This inhibition began 2-4.5 hr after the initiation of E2 infusion and was noted 1 to 3 weeks after subcutaneous implantation of E2-containing capsules. Pulse generator activity was also arrested during the initiation and subsequent development of estrogen-induced surges of luteinizing hormone. We propose that this inhibition of hypothalamic GnRH pulse generator activity by E2 in ovariectomized monkeys reflects the absence of an ovarian factor that normally protects this neuronal system from the inhibitory action of estrogen during the menstrual cycle.
Destruction of ovarian follicles during diestrus prolongs the lifespan of corpora lutea in cows, but the site(s) of action is unclear. Thus, ovarian follicles were destroyed in 10 beifers (X-IRRAD) on Day 9 postestrus, while 10 additional beifers (SHAM) served as a control group. To investigate changes in luteotropic support resulting from destruction of ovarian follicles, pulses of luteinizing hormone (LH) were characterized on Days 8, 13, and 15 postestrus. To study the interaction between products from ovarian follicles and prostaglandin F2 alpha (PGF2 alpha) in luteolysis, changes in serum concentrations of progesterone were monitored after an injection of saline or PGF2 alpha on Day 14 postestrus. Frequency and amplitude of pulses of LH increased by Day 13 in X-IRRAD beifers. An increase of similar magnitude in amplitude but not frequency of pulses of LH occurred between Day 13 and Day 15 postestrus in SHAM beifers. Exogenous PGF2 alpha was significantly less efficacious in causing luteolysis in X-IRRAD animals. We suggest that increased luteotropic support may be involved in but is not the only cause for lengthening the lifespan of corpora lutea following destruction of ovarian follicles. Additionally, we suggest that regression of bovine corpora lutea involves a synergistic action between products from ovarian follicles and PGF2 alpha.
The goal of this study was to pharmacologically block central nervous system (CNS) input to gonadotropes in mature ovariectomized gilts to determine the direct actions of estradiol (E2) on pituitary LH release when given at a dose sufficient to elicit a gonadotropin surge. Feeding AIMAX [N-methyl-N'-(1-methyl-2-propenyl)1,2-hydrazinedicarbothioamide; 125 mg/day] for 7 days reduced serum LH concentrations from 1.25 +/- 0.13 (mean +/- SE) to less than 0.18 ng/ml, abolished LH pulses, but did not compromise LH release in response to exogenous GnRH. Serum FSH concentrations were reduced by 27%, whereas serum concentrations of PRL, GH, thyroid hormones and cortisol were not affected after 7 days of AIMAX treatment. Behavior was not altered, aside from a slightly reduced appetite. The LH surge that peaked 48-80 h after injecting E2 benzoate (E2B) into control gilts was blocked in five of eight gilts given AIMAX. Giving GnRH pulses (1 microgram every 45 min) to AIMAX-treated gilts restored mean serum LH concentrations as well as the frequency and amplitude of LH pulses to those of untreated ovariectomized gilts. E2B suppressed the LH response to these GnRH pulses by 88% at 12 h, whereas from 24-96 h after E2B treatment, the LH response to GnRH and mean serum concentrations of LH were again similar to those of controls not given estradiol. These data indicate that induction of the gonadotropin surge by E2 in the gilt requires CNS input. The action of E2 on the pituitary in the presence of unvarying GnRH pulsation may, however, be limited to an early transient inhibition of responsiveness to GnRH, with no subsequent direct stimulation during the period of the surge.
The characteristic electrophysiological manifestations of LHRH 'pulse generator' activity were unaffected by prolonged elevations in plasma LH concentrations achieved by the administration of a long-acting LHRH agonist. These findings do not lend support to the existence of a 'short-loop feedback' inhibition of LHRH 'pulse generator' activity by LH.
In ovariectomized rhesus monkeys, the electrophysiological manifestation of luteinizing hormone-releasing hormone (LHRH) pulse generator activity was arrested by morphine and reinitiated by naloxone. These responses were noted within 1 and 2 min, respectively, after the intravenous injection of the drugs. Naloxone given alone had no effect. These results support the view that opioids modulate pulsatile gonadotropin release by an action on the hypothalamic LHRH pulse generator.
Abrupt increases in electrical activity can be recorded from the medial basal hypothalamus of the rhesus monkey and these bursts are correlated with a pulse of LH release from the anterior pituitary. In this study we have localized the tips of the electrodes from which such electrical activity can be recorded and have attempted to correlate the placement with the presence of immunoreactive LHRH neurons and axons. Electrodes associated with bursting activity were found as far rostral as the suprachiasmatic nucleus and as far caudal as the premammillary nuclei. The majority were found in the medial basal hypothalamus including the region of the arcuate nucleus, the retrochiasmatic zone and the dorsal aspect of the median eminence. The tips of the electrodes were associated with either LHRH neurons or axon bundles. Negative electrodes (those not associated with bursting electrical activity) which did not exit through the ventral surface of the brain nor enter the ventricle were found in the same regions of the hypothalamus as positive electrodes. Although it is tempting to associate the bursting electrical activity with the LHRH neurosecretory system, such a correlation cannot yet be made.
Characteristic increases in neuronal electrical activity associated with the initiation of each LH pulse were recorded from ovariectomized rhesus monkeys bearing multiple chronic electrodes in the medial basal hypothalamus. These electrophysiological manifestations of hypothalamic LHRH pulse generator activity were inhibited by the alpha-adrenergic blocker phentolamine or the alpha 1-adrenoceptor blockers phenoxybenzamine and prazosin. At the dosages used, the effects of single injections of these drugs ranged from a reduction in the frequency of LHRH pulse generator activity to its complete arrest. This was faithfully reflected in the pattern of pulsatile LH discharges. The dopaminergic blocking agent metaclopramide similarly reduced the frequency of the pulse generator or arrested its activity altogether. The alpha 2-adrenoceptor blocker yohimbine had no demonstrable effect on hypothalamic electrical activity at the doses studied. These findings support the view of a central action of alpha 1-adrenergic and dopaminergic blockade on LHRH pulse generator activity and the concept that central adrenergic and dopaminergic inputs can modulate the frequency of the LHRH pulse generator.
Characteristic increases in neuronal activity coincident with the pulsatile release of luteinizing hormone from the pituitary gland have been recorded from electrodes chronically implanted in the medial basal hypothalamus of the rhesus monkey. This electrophysiologic manifestation of the hypothalamic 'pulse generator' which governs the secretion of hypothalamic luteinizing hormone releasing hormone provides, for the first time, direct access to the central component of the neuroendocrine control system which regulates reproductive processes in this higher primate.
Objectives were to determine: 1) whether estradiol, given via implants in amounts to stimulate a proestrus increase, induces preovulatory-like luteinizing hormone (LH) and follicle-stimulating hormone (FSH) surges; and 2) whether progesterone, given via infusion in amounts to simulate concentrations found in blood during the luteal phase of the estrous cycle, inhibits gonadotropin surges. All heifers were in the luteal phase of an estrous cycle when ovariectomized. Replacement therapy with estradiol and progesterone was started immediately after ovariectomy to mimic luteal phase concentrations of these steroids. Average estradiol (pg/ml) and progesterone (ng/ml) resulting from this replacement were 2.5 and 6.2 respectively; these values were similar (P greater than 0.05) to those on the day before ovariectomy (2.3 and 7.2, respectively). Nevertheless, basal concentrations of LH and FSH increased from 0.7 and 43 ng/ml before ovariectomy to 2.6 and 96 ng/ml, respectively, 24 h after ovariectomy. This may indicate that other ovarian factors are required to maintain low baselines of LH and FSH. Beginning 24 h after ovariectomy, replacement of steroids were adjusted as follows: 1) progesterone infusion was terminated and 2 additional estradiol implants were given every 12 h for 36 h (n = 5); 2) progesterone infusion was maintained and 2 additional estradiol implants were given every 12 h for 36 h (n = 3); or 3) progesterone infusion was terminated and 2 additional empty implants were given every 12 h for 36 h (n = 6). When estradiol implants were given every 12 h for 36 h, estradiol levels increased in plasma to 5 to 7 pg/ml, which resembles the increase in estradiol that occurs at proestrus. After ending progesterone infusion, levels of progesterone in plasma decreased to less than 1 ng/ml by 8 h. Preovulatory-like LH and FSH surges were induced only when progesterone infusion was stopped and additional estradiol implants were given. These surges were synchronous, occurring 61.8 +/- 0.4 h (mean +/- SE) after ending infusion of progesterone. We conclude that estradiol, at concentrations which simulate those found during proestrus, induces preovulatory-like LH and FSH surges in heifers and that progesterone, at concentrations found during the luteal phase of the estrous cycle, inhibits estradiol-induced gonadotropin surges. Furthermore, ovarian factors other than estradiol and progesterone may be required to maintain basal concentrations of LH and FSH in heifers.
To study the mechanism by which estradiol induces a preovulatory surge of follicle stimulating hormone (FSH), we concluded experiments designed to determine: (1) the time course of change in luteinizing hormone releasing hormone (LHRH)-induced FSH release after estradiol in vivo, and (2) whether LHRH is required to trigger the FSH surge. Steers were given 1 microgram LHRH at 20-min intervals for 10 h, beginning 2, 8, 12 or 20 h after estradiol. During this period, serum samples were collected every 2 h (just before every sixth injection). The magnitude of LHRH-induced FSH release from baseline to peak was 40 ng/ml in oil-treated controls and increased (P less than .05) to 77 ng/ml when estradiol was given 2 h earlier. When LHRH was given starting at 8, 12 or 20 h after estradiol, the FSH response to LHRH was further augmented (P less than .001) so that the increment from baseline was about 150 ng/ml. To determine whether estradiol alters LHRH-induced FSH release in ovariectomized (ovx) cows as it does in steers, we gave ovx cows 1 microgram LHRH every 20 min beginning 2 or 8 h after estradiol. Serum samples were collected every 80 min (just before every fourth injection). When LHRH treatment began 2 h after estradiol, LHRH-induced FSH release was blocked (P less than .025) at 80 min after LHRH, but increased thereafter. When LHRH was given starting at 8 h after estradiol, concentrations of FSH increased 156 ng/ml above baseline. This release of FSH exceeded (P less than .001) the comparable value for cows given LHRH after oil (37 ng/ml). Furthermore, the LHRH-induced FSH release initiated 8 h after estradiol resembled the preovulatory and estradiol-induced FSH surges in magnitude (greater than 180 ng/ml), duration (8 to 10 h) and general shape. These results demonstrate that estradiol initially inhibits, then augments the capacity of the pituitary to secrete FSH in response to LHRH stimuli. The pituitary attains peak sensitivity long before the expected surge. Thus, we hypothesize that increased LHRH secretion triggers the FSH surge.
The objective was to determine how estradiol (0 vs 1 mg) and changes in the dosage of luteinizing hormone releasing hormone (LHRH; 1,000 ng/steer vs 1 ng/kg body weight) and frequency of LHRH injection (25 vs 50 min) affect LH and follicle stimulating hormone (FSH) release in steers. In steers pretreated with estradiol peak concentrations of LH in serum after LHRH averaged 14.4 ng/ml, which was greater (P less than .001) than peak concentrations in steers given oil (7.4 ng/ml). Increasing the dosage of LHRH from 1 ng/Kg body weight (approximately or equal to 300 ng/steer) to 1,000 ng/steer increased (P less than .001) peak LH values from 7.5 to 14.4 ng/ml. Furthermore, increasing the frequency of LHRH injections from once every 50 min to once every 25 min increased (P less than .001) LH release, but only in steers given estradiol. Estradiol reduced basal concentrations of FSH by 65% and then increased LHRH-induced FSH release by 276% (P approximately .07) relative to values for steers given oil. Only when 1,000 ng LHRH was given every 25 min to steers pretreated with estradiol were LH and FSH release profiles similar to the preovulatory gonadotropin surges of cows in magnitude, duration and general shape. The results demonstrate that increases in the dosage or frequency of LHRH pulses increase LHRH-induced release of LH, but not of FSH. Furthermore, these results are consistent with the hypothesis that in cows, estradiol increases responsiveness of the gonadotrophs to LHRH and then increases the magnitude and frequency of pulses of LHRH secretion beyond basal levels, thereby causing the preovulatory gonadotropin surges.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.