Faculty Bibliography

alpha MSH is present in high concentrations in the intermediate lobe of the fetal pituitary and has been implicated as a regulator of fetal adrenal steroidogenesis and fetal growth. However, there are few data regarding alpha MSH levels in fetal plasma or the control of fetal alpha MSH secretion. We measured alpha MSH immunoactivity in the plasma of chronically catheterized fetal lambs (gestational age, 116-138 days), newborn lambs, and adult sheep both in the baseline state and after dopamine receptor blockade with metoclopramide. The effect of metoclopramide on the release of another proopiomelanocortin-derived peptide, N-acetyl-beta-endorphin (N-acetyl-beta EP), which is synthesized together with alpha MSH in the intermediate lobe, was also studied. Baseline fetal plasma alpha MSH was significantly greater than maternal alpha MSH [35.6 +/- 2.2 (+/- SEM) vs. 10.0 +/- 1.0 pg/ml]. In eight studies in five fetal lambs, alpha MSH rose to a peak level of 121 +/- 23 pg/ml 15 min after metoclopramide administration to the fetus. Simultaneous maternal alpha MSH levels did not change, suggesting that the alpha MSH in fetal plasma was of fetal pituitary origin. Gel filtration of pooled fetal plasma extracts revealed that the alpha MSH immunoactivity eluted in the same position as the alpha MSH standard. Metoclopramide caused the secretion of nearly equimolar amounts of alpha MSH and N-acetyl-beta EP into fetal plasma. In four fetal lambs, basal N-acetyl-beta EP levels of 156 +/- 34 pg/ml rose to 305 +/- 65 pg/ml 15 min after metoclopramide treatment. Metoclopramide also stimulated plasma alpha MSH in newborn and adult sheep. In six newborn lambs, alpha MSH rose from 45.2 +/- 13 to 211 +/- 38 pg/ml 15 min after metoclopramide treatment, whereas in four adult sheep, a basal alpha MSH level of 11.1 +/- 2.2 pg/ml rose to 20.1 +/- 2.7 pg/ml 15 min after metoclopramide. In addition, metoclopramide stimulated fetal and neonatal PRL secretion, but had no effect on plasma vasopressin concentrations or acid-base and blood gas values. These studies indicate that immunoreactive alpha MSH and N-acetyl-beta EP are secreted into ovine fetal plasma and that the secretion of these peptides in the fetus appears to be under tonic dopamine inhibition, as is the case in the adult sheep and newborn lamb.

alpha-MSH and beta-endorphin, both synthesized from a common precursor, have opposite behavioral actions. In order to determine if these peptides have opposite effects on pituitary function, basal LH secretion and basal and stress-induced prolactin release were studied in adult male rats after intraventricular injection of alpha-MSH. Each rat also received intraventricular saline in order to serve as its own control. 18 micrograms alpha-MSH stimulated plasma LH from 16.5 +/- 2.5 (SEM) ng/ml to a peak of 27.2 +/- 4.0 and 26.0 +/- 4.9 ng/ml at 5 and 10 min, and suppressed prolactin from 3.5 +/- 0.7 ng/ml to 1.3 +/- 0.1 and 1.2 +/- 0.1 ng/ml at 15 and 30 min. Intraventricular alpha-MSH also significantly blunted the prolactin rise associated with the stress of swimming. 10 and 20 min after the onset of swimming, prolactin levels in rats pretreated with alpha-MSH were significantly diminished: 7.4 +/- 1.5 and 6.5 +/- 2.0 ng/ml vs 23.8 +/- 3.6 and 15.2 +/- 2.8 after normal saline. Similarly, des-acetyl alpha-MSH which is the predominant form of alpha-MSH in the hypothalamus, diminished the stress-induced prolactin rise from 18.4 +/- 5.3 and 11.2 +/- 3.4 ng/ml at 10 and 20 min to 10.0 +/- 2.4 and 5.5 +/- 1.6 ng/ml. We conclude that centrally administered alpha-MSH stimulates LH and suppresses basal and stress-induced prolactin release in male rats. These actions are opposite to those previously shown for beta-endorphin and suggest that alpha-MSH may antagonize the effects of beta-endorphin on pituitary function.

Several reports have shown that the prolactin response to suckling in rats can be blunted by administration of the opiate antagonist naloxone. In order to investigate whether the prolactin response to breast stimulation in women is similarly affected by naloxone, nine healthy lactating women participated in 10 studies. Each woman served as her own control and was studied on two occasions, receiving pretreatment with either saline solution or naloxone. Prolactin was measured in the baseline state and for 60 minutes after the onset of a 20-minute period of nipple stimulation by use of the Egnell mechanical breast pump. Neither baseline nor stimulated prolactin values were different by paired t test. Thus, in contrast to rats, an opioid pathway does not appear to be involved in the prolactin response to suckling in humans.

ACTH was measured with both C-terminal and midportion antibodies in monkey hypophyseal portal plasma, and compared to levels in monkey peripheral plasma, medial basal hypothalamus, and anterior pituitary. In nine female monkeys, mean hypophyseal portal blood C-terminal ACTH immunoactivity was 5290 +/- 2010 (SEM) pg/ml, whereas the mean midportion ACTH level was 949 +/- 178 pg/ml. These immunoactivities were not lower in two monkeys that were completely hypophysectomized 30 min before portal blood collection. The ratio of C-terminal to midportion ACTH immunoactivity was 4:1 in two monkey medial basal hypothalami, and 1:1 in four monkey anterior pituitary glands. Gel filtration of hypophyseal portal plasma extract and of medial basal hypothalamus showed that the C-terminal ACTH immunoactivity eluted in the same position as the corticotropin-like-intermediate lobe peptide standard. The similarity of the C-terminal to midportion ACTH ratios in monkey medial basal hypothalamus and portal blood, and the observation that ACTH immunoactivity was not significantly lower in two hypophysectomized monkeys suggests that portal blood C-terminal ACTH immunoactivity is of hypothalamic rather than pituitary origin. We conclude that monkey hypophyseal portal blood contains high levels of a C-terminal fragment of ACTH, which coelutes with corticotropin-like intermediate lobe peptide on gel filtration, and which is secreted from the brain directly into the portal circulation.

The records of 23 children with intrasellar and suprasellar neoplasms were reviewed for the results of endocrine evaluations before and after treatment with surgery, irradiation, and/or chemotherapy. Deficiency of at least one pituitary hormone was present in 13 patients before treatment and in 22 patients after treatment. Growth hormone deficiency, the most common endocrine abnormality in the pretreatment period, was present in 12 of 17 patients before treatment and in 17 of 21 patients after treatment. In the posttreatment period, thyroid-stimulating hormone deficiency was as common as growth hormone deficiency and was found in 17 of 21 patients evaluated. Hypothalamic-pituitary-gonadal dysfunction and deficiencies of adrenocorticotropic hormone and antidiuretic hormone also occurred in both the pretreatment and posttreatment periods, but were less common.