M. Clinton Miller

EXTRAPIGMENTARY EFFECTS OF MELANOCYTE-STIMULATING HORMONE IN AMENORRHŒIC WOMEN

Abstract Highly purified melanocyte-stimulating hormone (M.S.H.) was administered to six women with secondary amenorrhœa. Menstrual bleeding occurred in five of the patients approximately 13 days later. Transient electroencephalographic changes and akathisia-like symptoms developed in at least three of the women. The aqueous-flare phenomenon and increased visual dark adaptation were not observed, but statistically significant changes occurred in the concentrations of several components of serum.

General activity in intact and hypophysectomized rats after administration of melanocyte-stimulating hormone (MSH), melatonin, and Pro-Leu-Gly-NH2 ☆

Abstract The effects of melanocyte-stimulating hormone (MSH), melatonin, and Pro-Leu-Gly-NH 2 on levels of general locomotor activity were investigated in hypophysectomised and intact rats. General activity was not altered by the hormones studied. Body weight, food ingestion, and water intake were also measured and found to be unchanged. The findings reduce the possibility that alterations in activity account for the behavioral changes previously observed after administration of MSH, melatonin, or Pro-Leu-Gly-NH 2 .

Dose-Response Relationship of Luteinizing Hormone to Luteinizing Hormone-Releasing Hormone in Man

In previous clinical studies with highly purified porcine luteinizing hormone-releasing hormone (LH-RH), administration of the somewhat arbitrarily chosen doses of 700-1500 mug resulted in increased serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The present study determined the minimum effective dose as well as the relationship of the response of serum LH and FSH to the dose of LH-RH administered. Three normal men received i.v. injections of 1.1-810 mug of LH-RH. A dose of 10 mug of LH-RH caused a statistically significant elevation in serum LH. 30 mug of LH-RH significantly increased serum FSH levels. A highly significant linear trend was observed in the log dose-response curve. The results indicate that both LH and FSH release occurs in man with doses of LH-RH much lower than previously used and that a linear log dose-response relationship can be obtained.

Characterization of the hormonal responses to luteinizing hormone-releasing hormone (LH-RH) in prepubertal and adult subjects.

Extract: Luteinizing hormone-releasing hormone (LH-RH), purified from porcine hypothalamic tissue, was administered in an intravenous dose of 300

Melanin in the rat brain

mUg to four prepubertal and four adult human subjects. The resulting increases in plasma levels of LH and FSH were statistically significant (P < 0.01) in the 16− and 32-min samples, but did not differ with the age or sex of the subject groups. The mean maximum increase in plasma LH values was 290% for men and 425% for women. Injection of LH-RH resulted in a 500% mean maximum increase in LH levels in the plasma of boys and 850% in that of girls. The gonadotropin release induced by injection of LH-RH was sufficient to increase plasma levels of estradiol in some individuals. No significant elevation occurred in the levels in plasma of growth hormone, thyrotropin, or cortisol. It is concluded that LH-RH is a potent and specific hypothalamic releasing hormone for LH and FSH in prepubertal children as well as in normal adults.Speculation: The increases in gonadotropin levels in plasma of all groups seem to reduce the possibility that a change in pituitary responsiveness to LH-RH occurs at puberty. However, similar studies involving larger numbers of individuals tested at varying doses might reveal differences in responses to LH-RH between age or sex groups.

STIMULATION OF LUTEINISING HORMONE (L.H.) RELEASE AFTER ORAL ADMINISTRATION OF AN ANALOGUE OF L.H. RELEASING HORMONE

Melanin was measured in various parts of the rat brain by a spectrophotofluorometric assay. This method could detect natural, Sepia melanin as well as melanin synthesized from L-DOPA. Contrary to published expectations of other investigators, measurable amounts of melanin were found in the brain of albino as well as pigmented rats. The highest concentrations of melanin occurred in the pons-medulla and midbrain, but all regions within the blood-brain barrier contained greater concentrations than samples from many other tissues in the body. No significant change in the melanin content was found after various endocrine manipulations such as removal of the pituitary, pineal, adrenals, thyroid, testes, or ovaries, exposure to constant illumination or darkness, and daily injection for 5 weeks of alpha-MSH, Pro-Leu-Gly-NH2 (MIF-I) or melatonin. As expected, retinal tissue from black-hooded rats contained extremely high levels of melanin whereas that from albino rats contained no melanin. It is thought that the presence of melanin in the brain of albino and pigmented rats may have a function which is still unknown.

1357 MATERNAL RISK FACTORS IN VERY LOW BIRTHWEIGHT INFANTS

An analogue of luteinising-hormone-releasing hormone ([D-Leu-6, desGly-NH2-10]-L.H.R.H.-ethylamide) was administered by mouth to thirteen healthy men. In eight men 10 mg of this superactive L.H.R.H. analogue significantly increased mean plasma-L.H. within 45 minutes of administration. This increase was sustained for more than 5 hours. 2 mg of the analogue did not significantly increase plasma-gonadotrophin concentrations in the five men to whom this smaller dose was given. Oral administration of some L.H.R.H. analogues would seem to be effective in releasing L.H. in man.

MSH activity in plasma and pituitaries of rats after various treatments.

Newborns weighing under 1500 gm defy the ministrations of perinatologists and contribute heavily to the nations high perinatal mortality rate, yet, maternal risk factors for the birth of such infants have not been analyzed separately. To determine whether maternal factors associated with the delivery of very low birth-weight infants (VLBW) under 1500 gm are different from those associated with low birthweight infants (LBW) of 1500 to 2500 gm, prenatal data on 11,114 deliveries were evaluated. The sample included 435 VLBW infants. Maternal race, age, height, weight, gravidity, parity, past pregnancy performance and present pregnancy complications were analyzed using chi-square. Factors related to an increased incidence of VLBW but not of LBW infants were: 1) maternal age ≤ 15 years, ≥ 36 years, 2) gravidity over 8, 3) previous abortions, 4) previous fetal deaths, and 5) hypertensive vascular disease/essential hypertension. Race (black) and low prepregnancy weight were not related to VLBW but were associated with an increase in LBW. The finding that low prepregnancy weight is not related to VLBW implys that limited paturient mass is not a factor in supporting a fetus up to 1500 grams. The other positive findings suggest that suboptimal reproductive capacity and preexisting hypertension predispose to the birth of a VLBW rather than an LBW infant. These results contradict the concept of a uniform set of predisposing factors for the birth of all infants weighing ≤ 2500 gm.