Modulatory Effects Of Progesterone Research Articles

Progesterone effects on subjective and physiological responses to intravenous nicotine in male and female smokers

Previous studies suggest possible modulatory effects of progesterone on nicotine addiction. The goal of this study was to determine the effects of progesterone, on acute physiological and subjective responses to intravenous (IV) nicotine in overnight abstinent male and female smokers. Twelve smokers, six males and six females, participated in a double-blind, placebo-controlled, crossover study, which consisted of two experimental sessions. Before each session, subjects were treated orally with a single dose of either 200 mg progesterone or placebo. Starting 2 h following the medication treatment, subjects received an IV saline injection, followed by 0.5 and 1.0 mg/70 kg IV nicotine. Progesterone treatment, compared to placebo, enhanced the ratings of "bad effects," from IV nicotine and attenuated the rating of "drug liking." Progesterone also enhanced suppression of smoking urges by nicotine as assessed by the Brief Questionnaire on Smoking Urges (BQSU). These results suggest that progesterone may alter the subjective effects of nicotine as well as urges to smoke cigarettes. Further studies are warranted to examine the modulation of nicotine's effects by gonadal hormones.

The role of estradiol and progesterone in modulating the subjective effects of stimulants in humans.

Although stimulant abuse is a growing problem among women, few studies have focused on factors that may be implicated in potential sex differences. Numerous preclinical studies have indicated that female rodents are more sensitive than male rodents to the behavioral effects of stimulants and that the hormone estradiol is involved in these sex differences. In humans, the subjective response to stimulants is greater in the follicular phase (characterized by moderate estradiol levels and minimal progesterone levels) than in the luteal phase (characterized by elevated estradiol levels and elevated progesterone levels). Differences between men and women emerge only when men are compared with women in the luteal phase; the subjective response to stimulants is similar in men and women in the follicular phase. In contrast to rodents, there is minimal evidence that estradiol enhances the subjective response to stimulants in humans. Rather, the hormone progesterone has been shown to attenuate the subjective response to stimulants, particularly in women. Recent preclinical data confirm that progesterone reduces the behavioral response to stimulants. In summary, there is converging evidence from studies in humans that (a) men and women do differ in their subjective response to stimulants; (b) these sex differences are evident when women are in the luteal phase, when progesterone levels are elevated; and (c) progesterone administration attenuates the subjective response to stimulants. Therefore, the menstrual cycle should be addressed in mixed-gender studies. Moreover, the modulatory effects of progesterone on reducing the positive effects of cocaine may have some clinical utility in treating stimulant abusers.

Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro

Nitric oxide (NO) is produced in the CNS following injury-induced expression of inducible nitric oxide synthase (iNOS), yet its role as protective or damaging is unclear. Previous studies investigating the therapeutic potential of female sex steroids in stroke and trauma suggest that NO from this source is harmful, since oestradiol and progesterone decreased the level of iNOS expression in vitro and improved neurological outcome. We investigated the effects of progesterone on stroke-induced expression of iNOS in mice, as well as cytokine-induced expression of iNOS and its transcriptional activators in cells relevant to injury. We observed a significant reduction in stroke-induced iNOS transcript in progesterone-treated mice and in cultured macrophages. In contrast, progesterone significantly amplifed cytokine-induced iNOS mRNA in cultured primary astrocytes, although the expression of protein was decreased. We sequenced upstream of the 1.5 kb reported iNOS promoter region and identified a potential progesterone response element (PRE). Astrocytes transiently transfected with iNOS promoter/CAT reporter gene constructs containing the PRE displayed a significant increase in induction of CAT expression after progesterone treatment, and this was diminished in cells transfected with a construct containing a disrupted PRE. These observations suggest the involvement of iNOS in the neuroprotective effects of progesterone.

Identification of estrogen regulated genes in Fe33 rat hepatoma cells by differential display polymerase chain reaction and their hormonal regulation in rat liver and uterus

We applied the differential display RT-PCR (ddRT-PCR) technology to identify estrogen-regulated hepatic genes in the estrogen receptor expressing rat hepatoma cell line Fe33. Three genes of known sequences were detected by the ddRT-PCR approach: IGF binding protein-1 (IGFBP-1), vitamin D-dependent calcium-binding protein (CaBP9k) and major acute phase protein (MAP). Effects of ethinyl estradiol on the mRNA levels of these genes were confirmed by “Northern-blot” analysis. If given in combination with dexamethasone and glucagon, ethinyl estradiol caused 40-, 15- and 11-fold increases in the mRNA steady state level of IGFBP-1, CaBP9k and MAP, respectively, in Fe33 cells 24 h after addition of hormone. Besides ethinyl estradiol, the partial estrogen agonist OH-tamoxifen caused dose dependent effects on expression of MAP and IGFBP-1. Estrogen regulation of the respective genes and the modulatory effects of progesterone (10 mg/animal/day) were studied in ovariectomized rats treated subcutaneously for 14 days with 1 μg/animal/day estradiol. “Northern-blot” analysis of liver RNA revealed a 6-fold stimulation of IGFBP-1 mRNA levels in estradiol-treated compared to vehicle-treated rats and a weak but detectable increase of MAP mRNA steady state level (1.6-fold) upon estradiol administration. No effect of estradiol treatment could be monitored for CaBP9k in rat liver. Modulatory effects of progesterone on estradiol-stimulated expression in the liver could be monitored for IGFBP-1 only. In an extension of our investigation on the expression of the three genes in rat liver, we determined their expression and hormonal regulation in the uterus of the same animals. In the uterus, estradiol caused an increase in CaBP9k mRNA. In contrast, IGFBP-1 mRNA levels increased dramatically upon progesterone administration, whereas no effect of estradiol treatment could be detected. MAP mRNA levels increased only after coadministration of estradiol and progesterone. In conclusion, the ddRT-PCR proved to be a powerful method to identify estrogen-regulated genes. The study on the hormonal regulation of three genes stimulated by estrogen in Fe33 cells revealed similarities and differences in their regulation in vivo and in vitro.

Modulatory effects of progesterone upon dopamine release from the corpus striatum of ovariectomized estrogen-treated rats are stereo-specific

We have shown previously that progesterone linked with bovine serum albumin at position 3 of the progesterone molecule (P-3-BSA) was effective in modulating (both stimulating and inhibiting) amphetamine (AMPH)-evoked dopamine (DA) release in vitro from superfused corpus striatal (CS) tissue fragments of ovariectomized estrogen-primed rats. To examine the stereospecificity of this effect, progesterone linked with bovine serym albumin at position 11 (P-11-BSA) and deoxycorticosterone linked with bovine serum albumin at position 21 (DOC-BSA) were tested for their ability to modulate amphetamine-stimulated DA release in vitro when administered in either a pulsatile or a continuous infusion mode at different doses. The results demonstrate that a specific orientation of the P-BSA molecule is required for differential modulation of AMPH stimulated DA release from the CS of ovariectomized estrogen-treated rats, since DOC-BSA was ineffective and P-11-BSA showed only a stimulatory effect.