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Biomedical subjects

M Ferin

Publications and source records attributed to M Ferin.

At least 109 records · Page 6Linked to original sources

Estrogen-induced gonadotropin surges in female rhesus monkeys after pituitary stalk section.

In order to investigate the primary site of action of estradiol, whether pituitary or hypothalamic, gonadotropin responses to estrogen were studied in female rhesus monkeys before and immediately after pituitary stalk section. The estrogen challenge, consisting of either an injection of estradio benzoate (400 microgram) or an implant of three silastic capsules containing 17 beta-estradiol, was initiated on days 2--5 of the menstrual cycle. The estrogen was given not later than 8 h after stalk section. Estrogens induced LH surges in all five animals before and after stalk section. FSH increases were observed in four of five intact and three of four stalk-sectioned animals. Mean FSH and LH levels in three stalk-sectioned animals treated with oil alone did not differ significantly from preinjection controls. These experiments suggest that the locus of estrogens on gonadotropin release in the rhesus monkey may well reside within the pituitary gland itself.

Animals↗

Collection of blood from the pituitary stalk and portal veins in monkeys, and from the pituitary sinusoidal system of monkey and man.

A transorbital, transsphenoidal microsurgical approach to the pituitary stalk and gland was used to collect blood from the hypothalamo-hypophyseal portal system in monkeys. Specimens may be obtained from the entire pituitary stalk, individual long portal veins, or the pituitary sinusoidal bed, with little risk of mortality. Continuous stalk blood sampling was carried out for periods of up to 10 hours. Pituitary sinusoidal-system blood was also collected during transsphenoidal surgery in man. The uses of data concerning hypothalamic-hypophyseal regulation obtained by these methods are illustrated.

Animals↗

Neural control of gonadotropin secretion in primates.

In the rhesus monkey, there is abundant evidence to indicate that ovarian secretions, mainly estradiol-17beta, control "tonic" as well as "cyclic" secretion of gonadotropins during the menstrual cycle. This mechanism of control ensures coordination of ovarian morphology and anterior pituitary secretory patterns. The primary site of action of estradiol in controlling both "tonic" and "cyclic" secretion of gonadotropins has been circumscribed to the medial basal hypothalamic-pituitary unit. A modulatory role in "cyclic" secretion by neural structures situated within the anterior hypothalamic-preoptic area or by efferent fibers in passage through this region also has been postulated. However, the accrued evidence indicates that in the primate, contrary to the rodent, the role of these rostral neural structures is not essential for menstrual cyclicity. Strong evidence also indicates that the isolated pituitary gland can respond to estrogen signals as well. Secretion of gonadotropin-releasing hormone, the hypothalamic decapeptide, into the long portal vessels is, however, essential to maintain function of the gonadotroph. Further, pulsatile release of luteinizing hormone is distinctly under the control of a similarly paced hypothalamic clock.

Animals↗

Luteinizing hormone-releasing hormone in human pituitary blood.

Luteinizing hormone (LH) and LH-releasing hormone (LHRH) were measured by radioimmunoassay in blood samples collected from the pituitary gland during transsphenoidal surgery in 19 patients. Detectable levels of LHRH were present in 12 patients. Wide fluctuations of LHRH were seen in sequential samples collected at 10-minute intervals, suggesting a pulsatile mode of release. This technique may yield useful data on hypothalamic control of pituitary secretion.

Adolescent↗

The distribution of luteinizing hormone-releasing hormone (LHRH) in the hypothalamus of the rhesus monkey. Light microscopic studies using immunoperoxidase technique.

Neural structures containing LHRH were characterized in the hypothalamus of the rhesus monkey by four different antisera to the hormone and an immunoperoxidase technique. Immunoreactive perikarya were present in a continuum from the septal-preoptic region anteriorly to the premammillary nucleus posteriorly. These cells were more concentrated in the pericommissural and tubero-infundibular regions. Reactive axons in the median eminence appeared to originate from the positive perikarya in the medial basal hypothalamus; this projection forms a tubero-infundibular tract containing LHRH. In addition, substantial numbers of fibers which entered the median eminence continued down the infundibular stalk and into the posterior pituitary. Other axons appeared to originate in the pericommisural region and projected to the organum vasculosum of the lamina terminalis. Scattered positive fibers were also present in other hypothalamic areas, especially in the periventricular zone and medical mammillary nucleus.

Animals↗

Autoradiographic localization of hormone-concentrating cells in the brain of the female rhesus monkey.

With autoradiographic procedures, cells which bind 3H-estradiol were found in preoptic, hypothalamic and limbic structures in the brains of ovariectomized, adult female rhesus monkeys. Estrogen-binding cells were seen in the medial preoptic area, medial anterior hypothalamus, ventromedial nucleus, and especially heavy labelling was seen throughout the extent of the arcuate (infundibular) nucleus of the hypothalamus. In limbic structures, cells in the bed nucleus of the stria terminalis and in the medial nucleus of the amygdala were well labelled. Systematic charting also revealed smaller numbers of estrogen-concentrating cells in other specific hypothalamic and limbic locations. In the anterior pituitary, significant numbers of basophils and acidophils were found to bind estrogen. Pars intermedia and the posterior lobe were virtually unlabelled. In the uterus, heavily labelled cells were seen in the endometrial stroma and in the myometrium. These autoradiographic findings agree with results of parallel biochemical experiments. In monkeys injected with 3H-corticosterone, the most extensive high-intensity binding found with autoradiography was in the hippocampus. Both pyramidal neurons and dentate gyrus granule cells were labelled. Biochemical experiments, also, showed highest cell nuclear accumulation of corticosterone in the hippocampus. Findings with estradiol in the rhesus monkey extend to primates conclusions based on autoradiographic experiments with steroid sex hormones in wide variety of vertebrates, including fish, amphibians, birds, and various mammalian species (Morell st al., '75a). All of these vertebrate forms have sex hormone-concentrating neurons, which are found in specific preoptic, hypothalamic and limbic structures. In the species studied, such hormone-concentrating neurons appear to be involved in the hormonal control of behavioral and pituitary function.

Animals↗

Plasma neurophysin levels in monkeys: emphasis on the hypothalamic response to estrogen and ovarian events.

Specific radioimmunoassays for human neurophysins released in response to estrogen (estrogen-stimulated neurophysin, ESN) and nicotine (nicotine-stimulated neurophysin, NSN) have been used to measure two similar neurophysins in rhesus monkey plasma. As in the human, concentrations of rhesus monkey neurophysins in plasma were specifically produced a marked increase of plasma NSN concentrations in the monkey. Estradiol benzoate administered intramuscularly consistently produced an increase in plasma ESN concentrations in normal cycling and castrate monkeys. ESN response to estrogen was exclusively positive and occurred approximately 10 hours after an injection of estradiol benzoate intramuscularly. Plasma samples obtained throughout the mid-cycle were measured and a characteristic rise in estrogen and LH, and a more prolonged rise in ESN were found. Our data indicate that the ESN and LH responses to estrogen stimulation are temporally related events and that the assay of ESN in plasma may be of unique value as it directly reflects the hypothalamic response to changes in estrogen secretion.

Animals↗

Pituitary stalk portal blood collection in rhesus monkeys: evidence for pulsatile release of gonadotropin-releasing hormone (GnRH).

Hypothalamic-pituitary stalk portal blood was collected from 12 female rhesus monkeys. The pituitary stalk was approached transorbitally and cut at the level of the diaphragma sellae under direct visualization. After complete heparinization of the animal, stalk portal blood was obtained continuously, for periods of 30 minutes to 9 hours, using a constant exfusion pump at a rate of 30 to 40 mul/min. The mean GnRH in portal blood, as measured by radioimmunoassay, was 66 +/- 6.6 pg/ml (+/- SE) in 7 ovariectomized animals and 51 +/- 5.3 pg/ml (+/- SE) in 2 monkeys during the early follicular phase. Fluctuations in portal blood GnRH were most prominent in ovariectomized animals, with peak levels of 200-800 pg/ml and intervals of 1 to 3 hours between pulses. Peaks of GnRH during the early follicular phase did not exceed 200 pg/ml. The administration of estradiol (1000 ng, iv) to 3 monkeys did not decrease GnRH levels within the next 2 hours. These data provide direct evidence for a hypothalamic mediation of pituitary LH pulsatile release.

Animals↗

Suppression of prolactin secretion by L-dopa in the stalk-sectioned rhesus monkey.

The effects of iv administration of L-dopa on serum prolactin were studied in both normal female rhesus monkeys and in monkeys in which the pituitary stalk had been previously sectioned. Revascularization of the pituitary gland was prevented by the insertion of a silastic barrier over the diaphragma sellae. Prolactin secretion was increased in all stalk-sectioned monkeys and, in contrast to intact animals, chlorpromazine administration was ineffective in further releasing prolactin. In both normal and stalk-sectioned monkeys, iv administration of L-dopa (3-120 mg) significantly inhibited prolactin release from the pituitary (P less than .005 normal; P less than .001 stalk section). L-dopa also suppressed the TRH-induced release of prolactin in both groups. These results indicate that L-dopa or dopamine may act directly on the anterior pituitary to inhibit prolactin secretion.

Animals↗

Phencyclidine sedation as a technique for handling rhesus monkeys: effects on LH, GH, and prolactin secretion.

Rhesus monkeys, sedated with phencyclidine hydrochloride (Sernylan), were quieted for prolonged periods of time, while maintaining somatic reflexes, muscle tone, and respiration. Brief daily periods of sedation did not interfere with the menstrual cycle. Prolonged sedation, however, interfered with the experimentally estrogen-induced LH surge, but not with the inhibitory action of estrogen on LH tonic secretion. Pulsatile release of LH, GH, and prolactin persisted even under prolonged sedation. The secretion of prolactin in response to the administration of TRH was increased in animals sedated with phencyclidine.

Animals↗

Ovarian modulation of immunoreactive gonadotropins-releasing hormone (Gn-RH) in the rat brain: evidence for a differential effect on the anterior and mid-hypothalamus.

Gonadotropins-releasing hormone (Gn-RH) in selected regions of the female rat brain was measured by radioimmunoassay. Detectable immunoreactive Gn-RH was found in the anterior hypothalamic-septal region and in the mid-hypothalamic (arcuate-median eminence) region. Gn-RH was several times higher in the middle region than in the anterior region. Gn-RH was undetectable in the posterior hypothalamic region, frontal cerebral cortex and pineal glands, as well as in random blood samples, and low to undetectable in anterior pituitary glands. Gn-RH activity varied during the estrous cycle and after castration. In the mid-hypothalamic region, Gn-RH content was lowest throughout diestrus and in late morning and early afternoon of proestrus, and highest early in the morning of proestrus and during estrus. A significant decrease at mid-day was only found on the day of proestrus, a few hours prior to the critical period for LH release. In the anterior hypothalamic region, low Gn-RH activity was found from 1200 h of estrus to 1200 h of diestrus-2. A comparatively higher activity was seen at 1700 h of diestrus-2 and also from 1400 h of proestrus to 0800 h of estrus. Twenty-one days after ovariectomy, Gn-RH in the mid-hypothalamic region was significantly lower than the lowest values seen during the estrous cycle, while Gn-RH in the anterior hypothalamic region remained between low and high values seen during the cycle, being significantly higher than the low values. The changes observed during the estrous cycle and after castration suggest that gonadal steroids play a direct role in the control of hypothalamic Gn-RH. These data also demonstrate that Gn-RH varies in a different way in the anterior and mid-hypothalamic regions.

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