Sandra D. Michael

Estradiol down-regulates LPS-induced cytokine production and NFkB activation in murine macrophages

PROBLEM: In vivo and in vitro studies have indicated that estradiol can affect cytokine production in different cell types. This study examines whether estradiol affects inflammatory cytokine production by murine splenic macrophages.

Plasma Prolactin and Progesterone during the Estrous Cycle in the Mouse

Summary The concentrations of prolactin and progesterone in plasma of Line C mice during different stages of the estrous cycle were measured by radioimmunoassay. During the afternoon of proestrus, prolactin rose to a peak concentration at 1900 hr. The pattern of progesterone consisted of two major surges, beginning during the late afternoon of proestrus and the morning of metestrus. The author is indebted to Mr. Jerome J. Cymerman for assistance with the vaginal smears and to Dr. Y. N. Sinha for providing the materials for the radioimmunoassay of mouse prolactin.

Quantitative Changes in Macrophage Distribution in Normal Mouse Ovary Over the Course of the Estrous Cycle Examined With an Image Analysis System

PROBLEM: The current study considered the distribution of macrophages within the major ovarian structures throughout the estrous cycle.

Estrogen and thymic hormone interactions in the female mouse.

This study showed that there are relationships between thymic and adrenal/ovarian endocrine actions. A 4 mg/kg dose of thymosin fraction 5 (TSN5) advanced vaginal opening and elevated estrogen levels. Single estradiol benzoate (EB) injections decreased thymus weight and caused a transient reduction in circulating plasma levels of thymosine alpha 1 (TSN alpha 1), a peptide component of TSN5. Circulating estrogen levels were elevated when TSN alpha 1 levels were undetectable. Also, TSN alpha 1 levels decreased with age and after a prolonged athymic state. The thymus was shown to involute after a single TSN5 injection, suggesting the existence of a negative hormonal feedback on the thymus. Additionally thymectomy at 3 days of age was shown to delay vaginal opening while thymectomy at 30 days of age failed to produce any significant effect on reproductive maturation. Although much research is still needed, our results provide additional evidence of a relationship between the endocrine thymus and ovary.

Alteration of Cytokine Production in Follicular Cystic Ovaries Induced in Mice by Neonatal Estradiol Injection

PROBLEM: Neonatal estradiol injections in mice lead to follicular cystic ovaries that are similar to ovaries in patients with polycystic ovarian syndrome (PCOS). The present study examined ovarian cytokine production following neonatal estradiol injection.
 METHOD OF STUDY: Female (C3H/HeJ×129/HeJ)F1 mice were injected daily with 20 μg 17β‐estradiol from 0–3 days postpartum. At intervals, animals were sacrificed to determine ovarian architecture, circulating levels of estradiol, ovarian and peritoneal machrophage cytokine production, and ovarian P450 aromatase enzyme mRNA levels.
 RESULTS: Similar to PCOS, our results show that neonatally estradiol‐injected mice have lower levels of circulating estrogen that are correlated with decreased mRNA levels of P450 aromatase enzyme. Our data also show that follicular cystic ovaries have increased tumor necrosis factor (TNF)‐α and interleukin (IL)‐6 production. This increase in TNF‐α and IL‐6 production is also observed in peritoneal macrophages of estradiol‐injected mice.
 CONCLUSION: The present study showed that neonatal estrogen injection in mice has an overall systemic effect on cytokine production. We speculate that increased cytokine production may alter certain important steps in follicular maturation, ultimately contributing to ovarian dysfunction.

Analysis of steroid hormone levels in female mice at high population density

Populations of predominantly female house mice (Mus musculus) were created by placing virgin female mice in cages (0.045 m2 to 0.48 m2) with a single stud male, and removing all ensuing male offspring at weaning. At maximum population size, the females in these all-female/one-male populations exhibited male-like aggressive behavior. Termination of the populations and subsequent measurement of steroid hormone levels indicated that the aggressive females had high circulating level of testosterone and corticosterone, and elevated baseline levels of progesterone. The high levels of corticosterone could be lowered by dexamethasone, but not the high levels of testosterone.

Proposed mechanism for sperm chromatin condensation/decondensation in the male rat

Condensation of sperm chromatin occurs after spermatozoa have left the caput epididymis and are in transit to the cauda epididymis, during which time large numbers of disulfide bonds are formed. The formation of these disulfide bonds requires the repeated oxidation of the cofactor, NAD(P)H. To date, the means by which this oxidation is achieved has yet to be elucidated. Spermatozoa lose the bulk of their cytoplasm prior to leaving the testis; and, as a result, any shuttle systems for removing and transferring reducing equivalents into the mitochondria are unlikely to be operational. In an apparent preparation for the loss of cytoplasm, however, the following events occur during spermatogenesis. First, androgen-binding protein (ABP) is produced by the Sertoli cells of the testis; second, high affinity binding sites for ABP are inserted into the membrane surrounding the nucleus; and third, a nuclear location is acquired for the enzyme, 3α-hydroxysteroid dehydrogenase (3α-HSD).We propose that after the loss of cytoplasm, the nuclear region of spermatozoa is directly accessible to constituents contained in the lumen of the caput epididymis. As a consequence, luminal ABP attaches itself to the nuclear membrane via its binding sites, and is internalized. After internalization, ABP exerts its principle function, which is to bind to luminal 5α-dihydrotestosterone (5α-DHT), thereby ensuring its availability to the enzyme, 3α-HSD. In the conversion of 5α-DHT to 3α-androstanediol (3α-Diol), NAD(P)H is oxidized. Spermatozoa that reach the cauda epididymis have fully condensed chromatin. In addition, the nuclear region retains appreciable amounts of 5α-DHT and 3α-Diol, both bound to ABP. During fertilization, the bound 3α-Diol is converted back to 5α-DHT, reducing equivalents are transferred to NAD(P)+, and disulfide bonds are broken.IVF clinics report that spermatozoa with incompletely condensed chromatin have a low percentage of fertilization. If our proposed mechanism for chromatin condensation/decondensation is borne out by further research, IVF clinics might consider preincubating spermatozoa with 5α-DHT in order to increase the efficiency of fertilization.

Ergot drugs suppress plasma prolactin and lactation but not aggression in parturient mice

Abstract The daily administration of pituitary prolactin (PRL) inhibitors (ergocornine hydrogen maleate and 2-bromo-α-ergocryptine) to parturient Rockland-Swiss Albino mice suppressed circulating levels of PRL and lactation but failed to alter maternal aggression toward adult male intruders. The results suggest that, contrary to popular speculation, PRL may not be necessary for postpartum aggression in the mouse.

Differential effects of cannabinoid exposure and stress on plasma prolactin, growth hormone and corticosterone levels in male mice.

Abstract Plasma prolactin (PRL) levels were reduced in stressed and non-stressed male mice after a single dose of Δ 9 -tetrahydrocannabinol (THC), the main psychoactive constituent of marihuana, while growth hormone (GH) levers were reduced only in non-stressed animals. Chronic treatment with THC did not affect PRL or GH levels under either condition. Neither acute nor repeated exposure to THC affected plasma corticosterone levels. In contrast to the affects of THC, acute exposure to cannabinol (CBN), a non-psychoactive ingredient in marihuana, increased plasma GH levels in non-stressed mice, while repeated CBN treatments reduced GH levels in stressed animals. Moreover, chronic CBN exposure resulted in decreased peripheral levels of corticosterone in both stressed and non-stressed mice, and reduced plasma PRL levels in stressed mice. Psychoactive and non-psychoactive components of marihuana can exert different effects on endocrine function and on responsivity to stress in male mice.

Organophosphorus insecticide induced decrease in plasma luteinizing hormone concentration in white-footed mice

Oral intubation of 50 and 100 mg/kg acephate inhibited brain acetylcholinesterase (AChE) activity by 45% and 56%, and reduced basal luteinizing hormone (LH) concentration by 29% and 25% after 4 h in white-footed mice (Peromyscus leucopus noveboracensis). Dietary exposure to 25, 100, and 400 ppm acephate for 5 days substantially inhibited brain AChE activity, but did not affect plasma LH concentration. These preliminary findings suggest that acute exposure to organophosphorus insecticides may affect LH secretion and possibly reproductive function.