Ovarian steroid hormones and endometrial response

As a bioassay of the steroidogenic function of the corpus luteum, endometrial biopsy has been proposed as the most efficient way of diagnosing corpus luteum insufficiency. However, analysis of our data on luteal phase evaluation in infertility shows that most cases (86%) of endometrial luteal inadequacy are associated with normal hormone (progesterone, estradiol) stimulation. This apparent lack of endometrial progestational response may be explained by an end organ defect localized to the endometrial steroid receptors.     

Ovarian morphology of the Japanese eel in Mikawa Bay

Annual changes in gonadal maturation of female Japanese eel Anguilla japonica in sea water were investigated histologically over 5 years in the Mikawa Bay, Japan, where they occurred throughout the year except in March. Almost all immature Japanese eels (yellow eels) occurred mainly from April to September, and they were rare after November. In contrast, maturing Japanese eels (silver eels) occurred from October to February. The gonado‐somatic index ( I _G) and oocyte diameters of yellow eels were <1·0 and 150 μm, respectively, and oocytes were at the peri‐nucleolus or the oil droplet stages. The I _G and oocyte diameters of silver eels were greater than those of yellow eels and most oocytes developed to the primary yolk globule stage. The numbers of silver eels lacking oocytes at the primary yolk globule stage increased after January in Mikawa Bay, although I _G and oocyte diameters remained unchanged. In contrast, silver eels caught at the mouth of the bay in January possessed oocytes that had advanced to the secondary yolk globule stage. These observations indicate that oocyte development changes seasonally, especially after winter in Mikawa Bay.     

Ovarian steroid synthesis in tissue culture after administration of hormones and epidermal growth factor

The features of steroidogenesis of immature mouse ovaries in culture under the influence of follicle-stimulating hormones (FSH), human chorionic gonadotropin (hCG), epidermal growth factor (EGF) and insulin have been investigated during the period of reinitiation of meiosis in the oocytes. Secretion of progesterone is stimulated after addition of FSH, hCG and of insulin and EGF combination to the medium. EGF increases FSH-stimulated progesterone secretion and inhibits estradiol secretion. The ratios progesterone/estradiol and testosterone/estradiol increase, when EGF is added to the culture medium. It is analogous to the action of hCG. It is suggested that EGF may be an intrafollicular EGF regulator of luteinizing hormone action on the sex and somatic cells of the mammalian ovaries.     

Energetic challenges unmask the role of ovarian hormones in orchestrating ingestive and sex behaviors

Effects of ovarian hormones on sex and ingestive behavior are well studied, and yet, their role in diverting attention from food to sex has not been examined directly, possibly because these functions are masked under conditions of excessive food abundance typical of the laboratory. Female Syrian hamsters were either fed ad libitum or food-restricted to 75% of their ad libitum intake for 8 days and then tested every day of the estrous cycle for their preference for males versus food, food hoarding and food intake in an apparatus designed to mimic aspects of their natural habitat. The food-restricted, but not the fed females, varied significantly over the estrous cycle in appetitive behaviors, which included their preference for males versus food and in the amount of food hoarded, with low food hoarding and high male preference on the night of ovulation. In contrast, there were no significant differences between restricted and ad libitum-fed females in the consummatory behaviors, namely, food intake or lordosis duration. In ovariectomized females, estradiol plus progesterone treatment delayed food restriction-stimulated hoarding and hastened feeding-inhibited hoarding without affecting food intake or lordosis duration. In summary, energy restriction and the presence of males unmasked an effect that was obscured in the normal laboratory conditions characterized by isolation and an over abundance of readily available food. These results are consistent with the idea that ovarian hormones orchestrate appetites for food and sex to optimize reproductive success under fluctuating energetic conditions.     

Influence of sex steroid hormones on cerebrovascular function.

The cerebral vasculature is a target tissue for sex steroid hormones. Estrogens, androgens, and progestins all influence the function and pathophysiology of the cerebral circulation. Estrogen decreases cerebral vascular tone and increases cerebral blood flow by enhancing endothelial-derived nitric oxide and prostacyclin pathways. Testosterone has opposite effects, increasing cerebral artery tone. Cerebrovascular inflammation is suppressed by estrogen but increased by testosterone and progesterone. Evidence suggests that sex steroids also modulate blood-brain barrier permeability. Estrogen has important protective effects on cerebral endothelial cells by increasing mitochondrial efficiency, decreasing free radical production, promoting cell survival, and stimulating angiogenesis. Although much has been learned regarding hormonal effects on brain blood vessels, most studies involve young, healthy animals. It is becoming apparent that hormonal effects may be modified by aging or disease states such as diabetes. Furthermore, effects of testosterone are complicated because this steroid is also converted to estrogen, systemically and possibly within the vessels themselves. Elucidating the impact of sex steroids on the cerebral vasculature is important for understanding male-female differences in stroke and conditions such as menstrual migraine and preeclampsia-related cerebral edema in pregnancy. Cerebrovascular effects of sex steroids also need to be considered in untangling current controversies regarding consequences of hormone replacement therapies and steroid abuse.     

Changes in ovarian development and plasma levels of sex steroid hormones in the wild female Japanese sardine (Sardinops melanostictus) during the spawning period

In order to clarify the spawning pattern of Japaneses sardine ( Sardinops melanostictus ) during the spawning period, changes in ovarian histology, frequency distributions of oocyte diameter and plasma levels of oestradiol-17β (E₂) and 17 a ,20β-dihydroxy-4-pregnen-3-one (17 a ,20β-diOH-P) were examined in female fish captured in the region off Kyushu and Shikoku in Japan. With the development of the ovary, the gonadosomatic index (GSI) increased gradually and the size of oocytes became larger. When the GSI exceeded 13, the translucent hydrated eggs began to dominate and ovulation subsequently occurred. After ovulation, GSI decreased to less than 3. Post-ovulatory follicles were found only in the lower GSI ranges and atretic oocytes were always observed in the ovary. Plasma E₂ levels increased along with ovarian development but decreased after completion of yolk accumulation. On the other hand, 17 a ,20β-diOH-P showed the highest level just before and after ovulation. Ovarian histology and hormonal profiles suggest that the sardine spawns repeatedly during the spawning period. Based on the concentration of 17a,20β-diOH-P, the female Japanese sardine was estimated to ovulate before the middle of the night.     

The role of ovarian steroid hormones in the regulation of basal and stress induced absence seizures

Ovarian hormones play an important role in the regulation of absence seizures in patients as well as in animal models. The present study examined whether chronic progesterone exposure would induce tolerance for the occurrence of absence seizures and whether reduction in gonadal steroids (via ovariectomy) would alter the number of basal and stress induced absence seizures in WAG/Rij rats, a genetic model for absence epilepsy.

Methods

In Experiment 1, female WAG/Rij rats equipped with EEG electrodes received progesterone (P) (20 mg/kg) or cyclodextrin (CD, solvent) i.p. injections once a day for 3 days while a third group received CD injections on Days 1 and 2 and P on Day 3. The EEG was recorded on the day preceding the injections and at each day after injections. In Experiment 2, female WAG/Rij rats equipped with EEG electrodes, were ovariectomized (OVX) or sham operated. EEG recordings were made before and at the 4th, 8th, 10th, 20th, and 35th day after surgery. Rats were then exposed to three series of 10 foot-shocks (FS, 1.5 mA, 1 s) over 3 days. The EEG was recorded 1 h before and 2 h after each FS series.

Results

Tolerance developed after a single P injection and the effect of P on SWDs was facilitated by two preceding control injections. No differences were found between OVX and sham-operated females in the occurrence of SWDs either in resting conditions or after acute FS exposure. However, OVX females showed a more prominent day-to-day aggravation in SWDs after repeated FS administration.

Conclusions

The data suggest an important interaction between hormones of the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes in seizure control. On the one hand, stress interferes with and facilitates the acute effects of progesterone on the occurrence of SWDs and, on the other hand, rats with an intact hypothalamo-pituitary-gonadal axis can better regulate the stress response and develop tolerance to the stressor.     

Nocardia brasiliensis: in vitro and in vivo growth response to steroid sex hormones

As actinomycetoma is more frequent in males than in females, the possibility that hormones might modify theNocardia brasiliensis growth and the course of experimental actinomycetoma was explored. FiveN. brasiliensis strains were grown on Sabouraud agar containing estradiol, progesterone or testosterone, in 3 different concentrations. Colony diameters were measured weekly for 7 weeks.N. brasiliensis strains were also grown in Sabouraud broth containing hormones. Glucose concentration was measured weekly for 6 weeks. Finally, experimental actinomycetoma was produced in male and female hormone-treated mice. Invasion rate, plantar pad diameter and positive retrocultures were assessed. In vitro experiments showed that progesterone and testosterone inhibitN. brasiliensis growth, manifested by lower colony diameters and greater glucose concentrations. In vivo experiments demonstrated that estradiol limits actinomycetoma development. Progesterone and testosterone induced greater diameters of inoculated plantar pads and greater invasion rates with greater positive culture numbers than estradiol. Results partially explain the resistance of females to actinomycetoma.     

Involvement of steroid hormones on in vitro maturation of pig oocytes

The purpose of this study was to determine if the addition of steroid hormones into the culture medium could influence the in vitro maturation of pig oocytes. The cumulus-oocyte complexes (COCs). collected from follicles of 2-5 mm diameter, were matured in steroid-free medium supplemented with various concentrations of estradiol-17beta (0-3000 ng/ml), progesterone (0-5000 ng/ml) and testosterone (0-300 ng/ml). The COCs were cultured for 42 h, then fertilized in vitro. We analyzed nuclear and cytoplasmic maturation with lacmoid stain 20 h after in vitro insemination. We observed no significant effect (P > 0.05) on the percentage of oocytes completing nuclear or cytoplasmic maturation or the number of sperm penetrating each oocyte for any concentration of progesterone, estradiol-17beta or testosterone. Similarly, adding a combination of those hormones to the medium did not significantly (P > 0.05) affect any of the criteria. In order to determine if there was a possible secretion of steroids during maturation, we added COCs, denuded oocytes and stripped cumulus cells to drops of a steroid-free medium and cultured them for 42 h, after which we analyzed the medium, before and after culture, for the presence of progesterone, estradiol-17beta and testosterone by radioimmunoassay (RIA) analysis. COCs, as well as cumulus cells alone, secreted similar amounts of estradiol (43.3 and 37.5 pg/ml, respectively) and progesterone (4.24 and 4.79 ng/ml, respectively) into the maturation medium. A small amount of estradiol (28.8 pg/ml) was also detected when oocytes were cultured alone. These results indicate that no steroids need to be added to the maturation medium of pig oocytes and that the COCs secrete steroids during maturation. It is possible that the amounts produced by the COCs fulfill any requirement for steroids if these steroids are required for either nuclear or cytoplasmic oocyte maturation.     

Bone and cartilage responsiveness to sex steroid hormones.

Gonadal steroids influence the skeletal growth and metabolism both during the pubertal growth spurt and in adulthood with aging. It is now generally agreed that sex steroid effect on skeletal tissues is due to indirect and direct actions. In this presentation, in vitro effects of sex steroids on cartilage cells are reported by comparison with those observed on bone cells.     

Ovarian steroidogenesis during follicular maturation in the domestic fowl (Gallus domesticus)

The steroidogenic potential of various physiological compartments within the ovary of the hen were examined using in vitro systems. Three-hour incubations of individual whole small follicles (less than 1 mm-1 cm) or 100,000 collagenase-dispersed theca cells of the five largest ovarian follicles (F1-F5) were conducted in 1 ml of Medium 199 at 37 degrees C in the presence and absence of luteinizing hormone (LH) (0.39, 0.78, 1.56, 3.13 and 6.25 ng), progesterone (5 ng), and dehydroepiandrosterone (DHEA, 5 ng). Steroid output was measured by radioimmunoassay of incubation media. Progesterone was not produced by small follicles although they are a major source of DHEA and estradiol and a significant source of androstenedione. Output of DHEA, androstenedione and estradiol was highly stimulated by LH. The substrate for androstenedione and estradiol in small follicles is probably DHEA. Output of DHEA and androstenedione in theca cells of F2-F5 was stimulated by LH in a dose-related manner. A dose-response relationship between estradiol output and the concentration of LH in media was not apparent in theca cells from F2-F5. Steroidogenesis in theca tissue of large follicles occurs predominantly via the delta 4 pathway. The ability of these theca cells to metabolize progesterone to androstenedione is lost between 36 and 12 h before ovulation. Their ability to metabolize DHEA to androstenedione is still present 12 h before ovulation. Aromatase activity is significantly reduced between 36 and 12 h before ovulation. These data indicate that both large and small follicles can be stimulated by LH. The small follicles are the major source of estrogen. As the large yolky follicles mature, steroidogenesis shifts from the delta 5 to the delta 4 pathway. By 12 h before ovulation, the F1 follicle has lost the ability to convert progesterone to androstenedione. The inability of the largest ovarian follicle to convert progesterone to androstenedione contributes at least in part to the preovulatory increase in the plasma concentration of progesterone that generates the preovulatory LH surge by positive feedback.     

Involvement of sex steroid hormones in the early stages of spermatogenesis in Japanese huchen (Hucho perryi )

In higher vertebrates, considerable progress has been made in understanding the endocrine regulation of puberty; however, in teleosts, the regulatory mechanisms of spermatogenesis during the first annual cycle remain unclear. The present study was conducted to understand the regulatory mechanisms of spermatogenesis throughout the different stages of the first spermatogenic cycle and to check the ability of various steroids and hormones to induce in vitro spermatogonial proliferation in Japanese huchen (Hucho perryi ). The results indicate that the serum level of 11-ketotestosterone (11-KT) was positively associated with germ cell type; the level first began to rise with the appearance of late-type B spermatogonia and continued to increase gradually throughout the active spermatogenic stages and spermiogenesis, reaching a peak value 2 wk before spawning, and then declined. During the spermatogenic stages, the serum concentration of 17alpha,20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-DP) was undetectable. Only a small peak was detected with the appearance of spermatocytes and spermatids, and at the time of spawning, the level increased dramatically, reaching its maximum value with the onset of milt production. Despite the high variation in serum levels of 17beta-estradiol (E2) both between months and among the individuals, E2 was found during the whole reproductive cycle. From these results, we concluded that 1) 11-KT is necessary for the initiation of spermatogenesis and sperm production, and it probably plays a role in spermiation, 2) 17alpha,20beta-DP is essential for the final maturation stage, could play a significant role in the mitosis phase and meiosis process, and probably participates in the regulation of spawning behavior, and 3) estrogen is an indispensable male hormone that plays a physiological role in some aspects of testicular functions, especially during the mitotic phase. The three steroids were also able to induce DNA synthesis, spermatogonial renewal, and/or spermatogonial proliferation in vitro.     

Bone marrow transplantation restores follicular maturation and steroid hormones production in a mouse model for primary ovarian failure

Recent studies suggest that bone marrow stem cells (BMSCs) are promising grafts to treat a variety of diseases, including reproductive dysfunction. Primary ovarian failure is characterized by amenorrhea and infertility in a normal karyotype female, with an elevated serum level of follicle-stimulating hormone (FSH) and a decrease level of estrogen caused by a mutation in FSH receptor (FSHR) gene. Currently, there is no effective treatment for this condition. The phenotype of FSHR (-/-) mouse, FORKO (follitropin receptor knockout), is a suitable model to study ovarian failure in humans. Female FORKO mice have elevated FSH, decreased estrogen levels, are sterile because of the absence of folliculogenesis, and display thin uteri and small nonfunctional ovaries. In this study, we determined the effects of BMSC transplantation on reproductive physiology in this animal model. Twenty four hours post BMSC transplantation, treated animals showed detectable estroidogeneic changes in daily vaginal smear. Significant increase in total body weight and reproductive organs was observed in treated animals. Hemotoxylin and eosin (H&E) evaluation of the ovaries demonstrated significant increase in both the maturation and the total number of the follicles in treated animals. The FSH dropped to 40-50% and estrogen increased 4-5.5 times in the serum of treated animals compared to controls. The FSHR mRNA was detected in the ovaries of treated animals. Our results show that intravenously injected BMSCs were able to reach the ovaries of FORKO mice, differentiate and express FHSR gene, make FSHR responsive to FSH, resume estrogen hormone production, and restore folliculogenesis.     

Exercise and ovarian steroid hormones: their effects on mitochondrial respiration

The effect of exercise on mitochondria respiration was studied in gastrocnemius muscle of ovariectomized rats, pseudopregnant rats, and estrous rats. The estrous cycles were followed by vaginal smears. Rats were made pseudopregnant (PSP) by 45 s cervical stimulation with a glass rod on the day of estrous. The treadmill protocol (21 m/min, 10 grade uphill) induced a significant decrease in state 3 oxygen consumption (oxidative phosphorylation) in estrous (0.26 +/- 0.02 vs. 0.49 +/- 0.05 microatoms O min(-1) mg protein(-1)) and ovariectomized rats (0.18 +/- 0.03 vs. 0.40 +/- 0.03 microatoms O min(-1) mg protein(-1)). In contrast, pseudopregnant and progesterone-treated ovariectomized rats did not decrease state 3 nor state 4 respiratory rates. These results show that the effect of exercise on mitochondria respiration does vary according to the hormonal status.     

Direct transcriptional targets of sex steroid hormones in bone

The sex steroid hormones, androgens and estrogens, via their respective nuclear receptors, regulate bone mineral density in humans and mice. Very little is known about the direct targets of the androgen and estrogen receptors in bone cells. First, models of hormone and receptor deficiency in mouse and human bone are discussed. This review then focuses on the direct targets of the receptors in osteoblasts and osteoclasts. A direct target of a NR is defined here as a gene that is regulated by NR binding to the DNA (either through DNA binding or association with a DNA binding protein) at an enhancer or promoter of that gene. The experimental evidence that illustrates androgen and estrogen gene regulation in osteoblasts and osteoclasts will be summarized and compared with the phenotype of the hormones in vivo.     

Influence of sex steroid hormones on spatial memory in a songbird

In mammals, sex steroid hormones influence spatial learning and memory abilities but there are few data regarding such effects in birds. We investigated whether non-invasive sex steroid hormone treatment would affect spatial memory task performance of great tits (Parus major). For five consecutive days, birds were fed wax moth larvae injected with either 80 μg testosterone or 80 μg estradiol carried in peanut oil immediately prior to behavioral testing. During the 5 days prior to and the 5 days following hormone treatment, birds were fed vehicle-injected larvae. Both hormone manipulations resulted in an elevation of circulating hormone levels within 5 min of larva ingestion. This elevation was sustained for at least 30 min but had no short-term (<1 day) effect on spatial memory performance. However, performance tended to increase during the first 5 days of vehicle treatment and during both sex steroid treatments whereas it decreased during the 5 days of vehicle treatment following either hormone treatment. These results suggest that both hormones led to some improvement in spatial memory that declined once treatment ended. The great tit hippocampus was found to express androgen and estrogen receptors which would provide a direct site of sex steroid action.     

Morphological and histological changes in the swim bladder during maturation of the Japanese eel

Silver eels Anguilla japonica ( I _G 1·5–3·5) had more developed rete mirabile, gas gland and submucosa than yellow eels ( I _G 0·4–1·5) and the development of swim bladder components increased with sexual maturity only in the early maturation process ( I _G 3·5). These observations indicate that the Japanese eel develops its swim bladder in either the river or shallow sea water and leaves for the open sea after the swim bladder has become adapted to a deeper-sea environment.