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L S Frawley

Publications and source records attributed to L S Frawley.

99 records · Page 6Linked to original sources

Increased LH secretory response to LHRH after hypophyseal stalk-transection of monkeys.

Luteinizing hormone-releasing hormone (LHRH) will evoke large increases of circulating LH in all species tested except for the rhesus monkey. Indeed, in the present study we found that an intravenous injection of a relatively large dose of LHRH (20 micrograms) evoked only a small (2.2-fold) increase in plasma LH levels, as measured by the dispersed interstitial cell bioassay in 4 intact follicular phase monkeys. In contrast, 4 stalk-transected animals exhibited a significantly greater (19.9-fold) increase in plasma LH levels when treated with 20 micrograms of LHRH within 1 week after surgery. Qualitatively similar differences in responsiveness also existed between the two treatment groups with respect to FSH secretion. 2 stalk-transected monkeys treated with LHRH at weekly intervals for the first 4 weeks after surgery showed progressive declines in the LH secretory response approaching, eventually, that observed in intact animals. In 3 additional monkeys, initiation of estrogen maintenance therapy within 3 h of stalk transection, to achieve mid-follicular phase plasma levels of estradiol, totally abolished hyperresponsiveness to LHRH. Thus, the results of this study demonstrate that a transient increase in pituitary responsiveness to LHRH occurs after hypophyseal stalk transection in rhesus monkeys. Although the results indicate that this phenomenon can be accounted for, in large part, by the absence of estrogen feedback, they do not preclude the possibility that factors other than LHRH and gonadal steroids regulate gonadotropin secretion in monkeys.

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Stimulation of prolactin secretion in rhesus monkeys by vasoactive intestinal polypeptide.

Vasoactive intestinal polypeptide (VIP) is a potent stimulus for prolactin (PRL) release in rats. The purpose of this study was to test the effect of VIP on PRL secretion in rhesus monkeys and to identify its site of action. Three experimental models were used: (1) intact monkeys during the follicular phase of the menstrual cycle; (2) female, hypophyseal stalk-transected, ovariectomized monkeys (St-OVX), and 93) monkey pituitary tissue perifused in vitro. Initial serum concentrations of immunoreactive PRL were more than 10-fold higher for ST-OVX monkeys (52.4 +/- 10.4 ng/ml, X +/- SEM; n = 6) than for intact monkeys (4. 79 +/- 1.0 ng/ml; n = 10). Intravenous administration of VIP (20 micrograms/kg body weight) induced an elevation of circulating PRL in each of the intact and ST-OVX monkeys tested. On the average, VIP treatment evoked more than a 9-fold rise in serum PRL in intact monkeys (p less than 0.01) and more than a 2-fold increase in ST-OVX monkeys (p less than 0.01), while injection of vehicle alone did not affect PRL levels in either experimental group. Addition of VIP (5 x 10(-9) - 5 x 10 (-6) M) to medium perifusing monkey pituitary tissue in vitro stimulated PRL secretion both in the presence and in the absence of dopamine (2.5 x 10(-6) M). Furthermore, the in vitro potency of VIP was comparable, on a molar basis, with that of thyrotropin releasing hormone. Collectively, these results indicate that VIP is a potent stimulus for PRL secretion in monkeys which exerts its effect, at least in part, by a direct action at the pituitary level. Therefore, VIP should now be considered as a possible PRL releasing factor in primates.

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Dopamine in hypophysial stalk blood of the rhesus monkey and its role in regulating prolactin secretion.

Numerous studies are suggestive of dopamine serving as the hypothalamic PRL-inhibiting factor in the monkey. In the present study, we measured dopamine concentrations in plasma collected from the hypophysial stalk and determined whether those concentrations were sufficient to account for the inhibiting effect on PRL secretion exerted by the hypothalamus. First, we collected hypophysial stalk blood from seven follicular phase monkeys (four anesthetized with pentobarbital and three with phencyclidine) using a transorbital surgical approach. Dopamine concentrations, measured with a liquid chromatographic-electrochemical procedure, averaged 0.76 ng/ml in stalk plasma and less than 0.1 ng/ml in peripheral plasma collected contemporaneously. Next, we determined the rate of dopamine infusion required to produce peripheral plasma concentrations of dopamine similar to those measured in hypophysial stalk plasma. In seven monkeys, a dopamine infusion rate of 0.1 microgram/kg BW . min produced plasma dopamine concentrations of 0.62 ng/ml, whereas a 10-fold higher rate (1.0 microgram/kg . min) produced plasma concentrations of 1.95 ng/ml. Then, we infused these doses of dopamine into intact follicular phase animals, stalk-transected animals, and estrogen-treated stalk-transected animals to determine their effect on PRL release. The physiological dose of dopamine (0.1 microgram/kg . min) significantly suppressed plasma PRL levels in intact follicular phase animals and estrogen-treated stalk-transected animals but not in untreated stalk-transected animals. The higher rate of dopamine infusion (1.0 microgram/kg . min) was required to inhibit PRL release in the latter group. These results demonstrate that dopamine is secreted by the hypothalamus into hypophysial portal blood in quantities sufficient to account for much of the PRL-inhibiting activity known to be caused by the hypothalamus. Moreover, the results suggest that estrogen reinforces the inhibitory effect of dopamine on PRL release in primates, in contrast to its antagonistic effect in rodents. (Endocrinology 108: 489, 1981)

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Mode of gonadotropin secretion in infantile female rats and the role of estrogen in feedback regulation.

The temporal aspects of gonadotropin release were studied in infantile (14-day-old) female rats. Blood samples were collected using vena cava cannulae at 10-, 15-, 20-, or 30-min intervals and assayed for either LH alone or for both LH and FSH. Within individual animals, blood LH levels exhibited a degree of variability suggestive of a pulsatile release of the hormone. Wide fluctuations in circulating FSH were also observed, indicating that FSH might also be secreted in a pulsatile manner. Peak values for both gonadotropins were 2- to 5-fold higher than baseline levels. The majority of pups exhibited a nonrhythmic release of hormones. In some animals, LH and FSH appeared to be secreted in a temporally coincident manner. Administration of LHRH to cannulated pups evoked a simultaneous discharge of both gonadotropins. To determine whether endogenous 17 beta-estradiol (E2) plays a physiological role in the control of LH secretion in infantile rats, circulating LH levels were monitored in cannulated pups which had been treated twice daily with anti-E2 serum for 4 days. Passive immunization to E2 did not affect pulsatile LH secretion. Therefore, the results of this study demonstrate that in infantile female rats, LH is secreted in a pulsatile manner which is independent of E2 feedback regulation.

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Hypothalamic peptides affect the ratios of GH and PRL cells: role of cell division.

In the present study, we attempted to ascertain whether the differential effects of hypothalamic peptides (GRF, LHRH, CRF, TRH) on the proportions of GH and PRL secreting cells in culture were dependent upon cell proliferation. This was accomplished by chronically exposing rat pituitary cells to selected hypothalamic peptides in the presence or absence of cytosine arabinoside (an inhibitor of cell proliferation) and then measuring hormone release by plaque assays. Our results suggest that the effects of these peptides on the percentages of GH and PRL cells are manifest via both proliferation-dependent and proliferation-independent mechanisms.

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