Does ethanol inhibit LH secretion in the rat?

A prevailing view among those studying neuroendocrine effects of ethanol is that acute doses suppress luteinizing hormone releasing hormone (LHRH) secretion, and consequently inhibit luteinizing hormone (LH) release in the rat. This phenomenon has not been observed in primates, and has been thought to be a species difference. The experimental procedures, however, have involved ethanol administration by oral or intragastric (ig) routes in humans and monkeys, but intraperitoneal (ip) or carotid artery injection in rats. It has also been suggested that inhibition of LH secretion by ethanol in rats is mediated by endogenous opioid peptides (EOP), because the effect can be reversed by the opiate antagonist naloxone. An alternative explanation is that ip ethanol injection might stress rats sufficiently to activate hypothalamic-pituitary-adrenocortical (H-P-A) and EOP systems that are well known to inhibit hormonal activities of the hypothalamic-pituitary-gonadal (H-P-G) axis. Presented here are preliminary results from experiments with male rats. When ethanol is administered ig, under relatively stress-free conditions, it does not inhibit LH secretion in gonadally intact or castrated males. In contrast, ip injection of the same ethanol dose (2.0 g/kg body wt) causes pronounced inhibition of LH secretion and concomitant increases in plasma prolactin (PRL) and corticosterone--indicative of a stress response. Furthermore, when ip ethanol administration is preceded by intracerebroventricular (icv) injection of a corticotropin releasing factor (CRF) antagonist (alpha-helical ovine CRF residues 9 to 41), the effects of ethanol on LH and corticosterone are blocked. These results indicate that it may be stress, rather than ethanol per se, that inhibits LHRH and LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Marihuana smoking suppresses luteinizing hormone in women.

Smoking a single 1-g marihuana cigarette containing 1.8% delta 9-tetrahydrocannabinol induced a 30% suppression of plasma luteinizing hormone levels (P less than .02) in women during the luteal phase of the menstrual cycle. After marihuana placebo cigarette smoking, no luteinizing hormone suppression was observed in the same women under double-blind conditions. Marihuana may have adverse effects upon reproductive function during the luteal phase of the menstrual cycle as a consequence of gonadotropin inhibition.

Alcohol effects on luteinizing hormone-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone in female rhesus monkeys.

The effects of acute alcohol administration on anterior pituitary function were studied in eight female rhesus monkeys during the follicular phase of the menstrual cycle. Integrated plasma samples were collected for 80 min before and 120 min after nasogastric intubation of alcohol (2.5 or 3.5 g/kg) or isocaloric sucrose control solution. Synthetic luteinizing hormone-releasing hormone (LHRH; 100 micrograms i.v.) was then administered, and plasma samples were collected for an additional 180 min. After sucrose control administration, LHRH stimulated a significant increase in both LH (P less than .001) and follicle-stimulating hormone (FSH) (P less than .004) within 30 and 80 min, respectively. After alcohol administration, LHRH-stimulated LH increased significantly (P less than .001) within 15 min when blood alcohol levels averaged 184 ( +/- 14.3) and 276 ( +/- 14.9)mg/dl. However, FSH levels remained equivalent to base line after alcohol and LHRH administration. The prevention by alcohol of LHRH stimulation of FSH during the follicular phase suggests that alcohol may attenuate normal follicular maturation, which in turn could result in luteal phase inadequacy or anovulation, conditions often observed in alcohol-dependent women and in animal models of alcoholism.

Alcohol effects on luteinizing hormone and testosterone in male macaque monkeys.

The effects of alcohol (2.5 and 3.5 g/kg) on luteinizing hormone (LH) and testosterone were studied in adult male macaque monkeys under both basal and naloxone-stimulated conditions. Integrated plasma samples were collected at 30-min intervals for 90 min before nasogastric intubation of alcohol (2.5 and 3.5 g/kg) or a sucrose control solution, isocalorically equivalent to 2.5 g/kg of alcohol. Under basal (non-naloxone-stimulated) conditions, alcohol (2.5 or 3.5 g/kg) did not change LH levels significantly from prealcohol control levels. When basal testosterone levels were normal (600-1300 ng/dl), alcohol significantly suppressed testosterone levels in a dose-dependent manner. Testosterone levels decreased by 52% (P less than .05) within 30 min after a 3.5 g/kg dose of alcohol. As average blood alcohol levels increased to 400 mg/dl and above, testosterone levels fell monotonically and remained over 70% below base-line levels (P less than .01). After administration of 2.5 g/kg alcohol, testosterone levels were significantly suppressed within 90 min (P less than .05) and remained 52 to 63% below control levels (P less than .02-.05) as average blood alcohol levels increased to 300 mg/dl. However, when basal testosterone levels were abnormally low (100-200 ng/dl), alcohol had no effect on testosterone or LH. Naloxone stimulation was used to circumvent the high incidence of abnormally low testosterone levels observed. Naloxone (0.5 mg/kg i.v.) administration 90 min after alcohol (2.5 and 3.5 g/kg) or sucrose control administration significantly increased LH levels in comparison to base line (P less than .02-.001). LH reached peak values within 60 min after naloxone administration. A significant increase in testosterone (P less than .001) was observed 90 min after naloxone administration as LH levels began to decline. Alcohol (2.5 and 3.5 g/kg) did not attenuate or delay naloxone-stimulated increases in LH and testosterone in comparison to sucrose control conditions.

Perseveration of attention to conspecific odors and novel objects in castrated gerbils.

Castrated male and female gerbils were tested for odor preference and for attention to conspecific odors and a novel object. Castrated gerbils housed with sham-operates preferred home odors, discriminated between two groups of male gerbils by olfactory cues, and perseverated in attention to odors of male gerbils and to a novel object. Similar perseveration to male conspecific odors was shown in gerbils given injections of L-DOPA (30 mg/kg). Combined treatment (castration and L-DOPA) resulted in additive effects on perseveration. This research challenges two general hypotheses of gonadal hormone function. The first, that changes in odor preference after castration are due to a loss in testicular androgen, is insufficient, because (1) female as well as male gerbils showed similar perseveration to odors, (2) there was a significant correlation between LH and duration of investigation of male conspecific odors, and (3) L-DOPA, the dopamine precurser, also caused perseveration to conspecific odors. The second, that gonadal hormones are responsible for persistence of attention, cannot be broadly generalized, because castration with resultant elevation of LH and regression of ventral glands resulted in perseveration of attention in male and female gerbils.

Blood alcohol levels as a function of menstrual cycle phase in female macaque monkeys.

Female Macaque monkey were given a low (1.5 g/kg), moderate (2.5 g/kg) and high (3.5 g/kg) dose of alcohol via nasogastric intubation. Integrated plasma samples for blood alcohol analysis were collected at 30 minute intervals over 210 minutes. Peak blood alcohol levels measured at the premenstruum, menstruation, the periovulatory and mid-luteal phase of the menstrual cycle did not differ significantly after a standard dose of alcohol. Average peak blood alcohol levels, independent of menstrual cycle phase after low, moderate and high doses of alcohol were 139, 238 and 335 mg/dl. Menstrual cycle phase was verified by calendar and radioimmunoassay of levels of luteinizing hormone and 17-beta estradiol. We conclude that in alcohol-naive female Macaque monkeys studied under controlled conditions, peak blood alcohol levels after a standard dose of alcohol do not vary as a function of phase of the menstrual cycle.

Effect of acute ethanol ingestion on integrated plasma prolactin levels in normal men.

Healthy male subjects ingested 1.0 g ethanol/kg (Alcohol Day) and caloric equivalents of sucrose (Control Day). Plasma prolactin was determined on samples collected at 20-min intervals by serial constant blood exfusion, from 2 hr before to 4 hr after the drink. In 14 of the 15 men studied, plasma prolactin levels during the 2-hr period after alcohol administration were elevated an average of 31% above values for the preceding 2-hr period. Data pooled for all subjects revealed a small but statistically significant increase in prolactin coinciding with ascending and peak concentrations of blood alcohol. A significant increment in prolactin was associated with peak blood alcohol levels when values were compared between control and alcohol treatment days. Although of statistical significance, these transient and variable increases were within the normal range of basal prolactin levels for most subjects and are unlikely to be physiologically meaningful.