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Biomedical subjects

E Knobil

Publications and source records attributed to E Knobil.

At least 55 records · Page 3Linked to original sources
PubMed1984

Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey.

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.

Anesthesia↗
PubMed1983

Hypophysiotropic signal frequency and the functioning of the pituitary-ovarian system in the rhesus monkey.

In adult rhesus monkeys bearing hypothalamic lesions that abolished secretions of LH and FSH, normal circulating levels of these hormones and consequent follicular development culminating in ovulation were reestablished by the administration of a GnRH pulse once every hour (control frequency). We examined the effects of slowing the frequency of these pulses on ovarian follicular development, as assessed by circulating concentrations of estradiol. A reduction in frequency to one pulse every 90 min supported follicular development in most instances, albeit with a diminished incidence of ovulation. One pulse of GnRH every 2 h resulted in anovulatory follicular cycles with lower peak concentrations of estradiol than those achieved on the control frequency. Follicular development was absent when GnRH pulses were delivered once every 3 h. When mean concentrations of gonadotropins were determined during periods of low circulating estradiol levels, plasma FSH concentrations in monkeys receiving GnRH pulses at the slow rates did not differ from control, whereas LH concentrations were significantly reduced. It can be concluded that small reductions in the frequency of GnRH stimulation have profound effects on the quality of follicular development, even when FSH concentrations are maintained at normal levels.

Animals↗
PubMed1982

Acute effects of N-methyl-DL-aspartate on the release of pituitary gonadotropins and prolactin in the adult female rhesus monkey.

The acute effects of an aspartic acid analogue, N-methyl-DL-aspartate (NMA), upon the release of several anterior pituitary hormones were examined in adult female rhesus monkeys. Intravenous injection of NMA (15 mg kg body weight) induced a large and rapid rise in plasma levels of luteinizing hormone, follicle stimulating hormone, and prolactin. Thyroid stimulating hormone concentrations were not altered. Thus, in primates, as in rodents, systemically administered NMA is capable of eliciting pituitary hormone secretion, although the site of its action in the rhesus monkey remains to be established.

Animals↗
PubMed1982

Relation between levels of circulating ovarian steroids and pituitary gonadotropin content during the menstrual cycle of the rhesus monkey.

Anterior pituitary glands were removed from 27 intact cycling rhesus monkeys sacrificed in the early (Day 2), mid (Days 6--9) and late (Days 11--12) follicular phase, and in the early and late luteal phase (3--5 and 10--15 days after the midcycle luteinizing hormone (LH) surge). Assignment of cycle stage was confirmed by the pattern of circulating steroid and gonadotropin levels seen in the blood samples taken daily throughout the cycle. The anterior pituitary glands were weighed, stored at -30 degrees C and assayed for LH and follicle-stimulating hormone (FSH) content by specific radioimmunoassays. Serum estradiol levels and pituitary LH and FSH contents rose simultaneously during the follicular phase. After the preovulatory gonadotropin surge, pituitary LH content was low and invariant. Pituitary FSH content reached a nadir in the early luteal phase and tended to rise in the late luteal phase. Multiple correlation analyses revealed that there is a positive correlation between rising levels of estradiol in the circulation and pituitary LH (p = 0.003) and FSH (p = 0.017) content, and that there is a significant negative correlation between circulating progesterone levels and pituitary FSH content (p = 0.002). Pituitary LH content is less strongly related to circulating progesterone levels. There was no significant difference in the wet weights of the anterior pituitary glands during the five phases of the menstrual cycle studied.

Animals↗
PubMed1982

Mode of action of progesterone in the blockade of gonadotropin surges in the rhesus monkey.

The action of progesterone (P) to block estradiol-induced gonadotropin surges in the rhesus monkey requires an intact hypothalamus. The present study was performed to determine whether the blocking action of P is the result of an inhibition in hypothalamic GnRH secretion or of some other mechanism. Ovulatory menstrual cycles were initiated in acyclic rhesus monkeys with intact nervous systems by a pulsatile GnRH replacement regimen previously shown to be effective in sustaining normal ovarian cycles in monkeys with hypothalamic lesions. Whereas unambiguous surges of LH and FSH were elicited by estradiol benzoate during the follicular phase of these cycles, no such gonadotropin discharges were obtained in the presence of luteal phase levels of P generated by sc P-containing Silastic capsules. Because exogenous GnRH replacement was provided throughout these experiments, it is concluded that P blockade of estradiol-induced gonadotropin surges is not the consequence of an interruption in GnRH release. The results suggest, rather, that P may cause the production of an inhibitory factor from the central nervous system which blocks the positive feedback action of estradiol on the pituitary gland.

Animals↗
PubMed1981

Differential effects of progesterone on secretion of gonadotropic hormones in the rhesus monkey.

To obtain new information on the site of the inhibiting actions of progesterone (P) during the follicular phase of the cycle, we administered P continuously to 13 rhesus macaques (Macaca mulatta) from days 5 through 12 of the menstrual cycle. This treatment produced luteal-phase levels (approximately 6 ng/ml of serum) within 4 h. (FSH) concentrations dropped significantly from pretreatment amounts (P less than 0.01). During this time, both immunoreactive luteinizing hormone (LH) (n = 8 animals) and bioactive LH (n = 5) remained stable. The 17 beta-estradiol (E2) concentrations dropped significantly below base line 24 h after treatment (P less than 0.05). The decline in E2 occurred after the decline in FSH. Inhibition of FSH continued for 40 h, after which both FSH and LH rose steadily in a way that resembled a preovulatory surge on days 8 or 9 of the menstrual cycle, and then returned to base line by day 10. When gonadotropins were at their zenith, the ovary did not respond by secreting E2. None of the effects mentioned above were found in control animals treated with blank implants. These data demonstrate that P administered during the follicular phase inhibits FSH but not LH secretion. This initial inhibition probably occurs at a hypothalamic-pituitary site, but after 40 h direct inhibitory effects on the ovary cannot be ruled out. P stimulates the release of gonadotropin in female monkeys despite reduced production of E2 by the ovary.

Animals↗
PubMed1981

The sites of action of ovarian steroids in the regulation of LH secretion.

In the monkey, estradiol appears to exert both its negative and positive feedback actions on gonadotropin secretion primarily at the hypophysial level. In the rat, inhibitory and stimulatory effects of estradiol on the pituitary are also evident, but additional actions on the medial basal hypothalamus (MBH) and preoptic area must be postulated to fully account for the negative and positive feedback effects of estradiol in this species. The available evidence points to the MBH as a site for the negative feedback action of progesterone in the rat. In both species, progesterone probably acts in the central nervous system to block the positive feedback action of estradiol while the facilitation of luteinizing hormone release by this steroid appears to be at a hypophysial level.

Animals↗
PubMed1981

Estradiol as a gonadotropin releasing hormone in the rhesus monkey.

The temporal relationship between cessation of GnRH delivery to the pituitary gland and the loss of responsiveness to the stimulatory action of estradiol (E2) was examined in 4 ovariectomized rhesus monkeys whose endogenous GnRH production had been abolished by hypothalamic lesions. Gonadotropin secretion was re-established by the intermittent administration of GnRH. The GnRH-replacement regimen was then discontinued and estradiol benzoate (EB) injected 24, 48, 72 and 96 hours later. Unambiguous gonadotropin discharges were induced when EB was administered 24 or 48 hours after discontinuation of GnRH replacement. We conclude that E2 can initiate gonadotropin discharges in the absence of circulating GnRH. E2 may, therefore, be viewed as a gonadotropin releasing hormone.

Animals↗
PubMed1981

Frequency and amplitude of gonadotropin-releasing hormone stimulation and gonadotropin secretion in the rhesus monkey.

In adult ovariectomized rhesus monkeys bearing hypothalamic lesions which reduced circulating LH and FSH to undetectable levels, sustained elevated gonadotropin concentrations were reestablished by the intermittent administration of gonadotropin-releasing hormone (GnRH) at the rate of 1 microgram/min for 6 min once every hour. The effects of varying either the frequency or the amplitude of these GnRH pulses on gonadotropin secretion were examined in such animals. Increasing the frequency of GnRH administration from the physiological one pulse per h to two, three, or five pulses h while maintaining a constant infusion rate and pulse duration resulted in gradual declines in plasma gonadotropin concentrations. These declines were most profound at the highest frequencies and the consequence of reduced pituitary responses to individual GnRH pulses. Decreasing the frequency of GnRH pulses from one per h to one every 3 h led to variable declines in plasma LH levels, but circulating FSH invariably rose. Reducing the GnRH infusion rate from 1 to 0.1 mg/min while maintaining constant frequency and pulse duration resulted in abrupt declines in plasma LH and FSH to immeasurable levels, although pulsatile increments in circulating GnRH concentrations without a concomitant reduction in plasma LH concentrations, which remained unchanged. An infusion rate of 0.5 microgram/min resulted in unstable plasma LH and FSH levels. These results demonstrate that changes in the frequency or amplitude of hypophysiotropic stimulation have profound effects on plasma gonadotropin levels as well as on FSH to LH ratios in the circulation. The physiological implications of these observations are discussed.

Animals↗
PubMed1981

On the site of action of progesterone in the blockade of the estradiol-induced gonadotropin discharge in the rhesus monkey.

The site of action of progesterone (P) in the blockade of estradiol-induced gonadotropin discharges was examined in rhesus monkeys bearing hypothalamic lesions which abolish endogenous GnRH production. Normal ovulatory menstrual cycles were re-established in these animals by the pulsatile, hourly administration of GnRH. In the follicular phase of these induced menstrual cycles, P-containing Silastic capsules were implanted sc yielding luteal phase plasma P concentrations which normally block estradiol-induced gonadotropin surges. P failed to block estradiol-induced surges in lesioned animals on GnRH replacement. In such animals, however, P advanced the initiation of these surges. While estradiol acts on the pituitary to cause gonadotropin discharges, P appears to block this effect by acting on the central nervous system. On the other hand, the results also suggest that the site of facilitatory action of P on gonadotropin release is at the level of the pituitary gland.

Animals↗