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Biomedical subjects

M Ferin

Publications and source records attributed to M Ferin.

At least 19 recordsLinked to original sources

The pars tuberalis of the rhesus monkey secretes luteinizing hormone.

The presence of luteinizing hormone within the pars tuberalis of the adenohypophysis and its secretion into pituitary stalk vessels were investigated in adult rhesus monkeys. Portal blood was collected in 9 monkeys, after section of the pituitary stalk. In 22 out of 26 samples, portal to peripheral LH ratios, as measured by radioimmunoassay, ranged from 2 to 48. Portal LH levels were highest in 3 animals studied at the time of the midcycle surge. No differences between portal and peripheral growth hormone (GH) and prolactin levels were observed. Immunocytochemical studies in 4 normal and 3 ovariectomized female monkeys indicated that LH, but not GH, prolactin or thyroid stimulating hormone were present within the pars tuberalis. Cells containing these hormones were identified within the pars distalis. These results indicate that the pars tuberalis forms and secretes LH via the hypophyseal portal circulation.

Animals

Regeneration of the magnocellular system of the rhesus monkey following hypothalamic lesions.

The hypothalamic magnocellular system of the rhesus monkey was studied with specific immunocytochemical techniques in animals that had undergone hypothalamic lesions. The results indicate that this system maintains a regenerative capacity even when its tracts are interrupted within the hypothalamus. New neurohemal units are reconstituted from newly formed vessels within the scar as well as from preexistent blood vessels, such as perforating and pial arterioles, and the vessels of the pars tuberalis of the pituitary gland, which normally do not contain neurosecretory terminals.

Animals

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