Differences in the rabbit uterine response to progesterone as influenced by growth hormone or prolactin

The direct effect of growth hormone (GH) on the uterine response to progesterone was tested by using ovariectomized rabbits (at least 12 weeks) treated with GH; GH + progesterone; or progesterone alone. These results were compared with the effect of prolactin or prolactin + progesterone on the uterus. Prolactin treatment produced an increase (P less than 0.01) in the endometrial surface area and restored cytosolic oestrogen and progesterone receptor concentrations to oestrous control values. The sequential treatment of does with prolactin + progesterone stimulated uteroglobin production to a concentration equal to that found in intact rabbits on Day 5 of pregnancy. In contrast, GH treatment had no effect on endometrial surface area, produced an increase in the concentration of cytosolic oestrogen receptor but did not produce an increase in the concentration of progesterone receptor. The sequential treatment of does with GH + progesterone failed to stimulate uteroglobin secretion above control (progesterone alone) values. It is concluded that the action of prolactin in the rabbit uterus is no generally somatogenic; rather, prolactin increases the concentration of progesterone receptor and thereby enhances the uterine response to progesterone.     

Prolactin as a factor for increased platelet aggregation

Administration of antipsychotics appears to be related to increased risk of venous thromboembolism and cerebrovascular side effects. The biological mechanism responsible for this possible adverse drug reaction is unknown, but there is a growing number of elucidating hypotheses. Treatment with antipsychotics is associated with elevation of prolactin level. Prolactin has recently been recognized as potent platelet aggregation co-activator, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. We briefly review the arguments for the role of hyperprolactinemia in pathogenesis of platelet aggregation.     

Prolactin response to beta-endorphin in man

Beta endorphin was administered intravenously to six medication-free schizophrenic patients under placebo-controlled conditions. Serum prolactin (PRL) and growth hormone (GH) concentrations were measured for 90 minutes after infusion. Prolactin was significantly increased following beta-endorphin infusion compared to placebo infusions. Growth hormone levels were not affected by beta-endorphin. The implications of the PRL response in schizophrenic patients await further study.     

Correlation between uterine weight and endometrial development in rabbits treated with progesterone]

Progesterone induced effect on rabbit uterus follows a log dosis endometrial glandular changes linear relationship and log dosis-organ weight one. It appears a strong correlation between endometrial changes and organ weight. Thus organ weight may be looked like a pseudogestative activity test, histological investigation remaining the actual proof of specific activity. Besides these relations bring direct informations on the quality of new progestatives.     

Effects of progesterone on growth factor expression in human uterine leiomyoma

It is now evident that the use of levonorgestrel-releasing intrauterine system (LNg-IUS) is effective for long-term management of menorrhagic women with uterine myomas because of a striking reduction in menorrhagia. This prompted us to characterize the effects of progesterone (P4) on the growth and apoptosis of uterine leiomyoma cells. On the other hand, we have recently noted that epidermal growth factor (EGF) and IGF-I play a crucial role in prompting uterine leiomyoma growth through stimulating the proliferative potential and inhibiting apoptosis of cultured human leiomyoma cells. In the present review, attention was paid to evaluate the effects of P4 on the expression of growth factors (EGF, IGF-I) and apoptosis-related factors (TNFalpha, Bcl-2 protein) in cultured uterine leiomyoma cells. Treatment with P4 augmented EGF and Bcl-2 protein expression, but inhibited IGF-I and TNFalpha expression in cultured leiomyoma cells. It is known that TNFalpha induces apoptosis in a variety of cell types and Bcl-2 protein is an apoptosis-inhibiting gene product. Thus, the results obtained suggest that P4 has dual actions on uterine leiomyoma growth: one is to stimulate leiomyoma cell growth and survival through up-regulating EGF and Bcl-2 protein expression as well as down-regulating TNFalpha expression in those cells, and the other is to inhibit leiomyoma cell growth through down-regulating IGF-I expression in those cells. This may explain why the size of uterine myomas during use of LNg-IUS increases in some but decreases in other instances. This may also explain why the size of uterine myomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones.     

Prolactin as a luteotrophin

This review summarizes evidence suggesting a direct luteotrophic role for the hypophyseal hormone prolactin (PRL). This direct role consists of the capability to stimulate progesterone synthesis in vitro, the capability to maintain the membrane fluidity and receptors for luteinizing hormone and the capability to import substrate for progesterone synthesis. The time required for PRL-induced luteotrophic events is in the order of hours and sometimes days, and it appears that the effects are not associated with acute intracellular changes. The relatively slow responses and the stimulation of specific protein synthesis by PRL in target tissues other than the ovary suggest that PRL may function primarily through activation of the genome. PRL may induce the synthesis of specific luteal proteins, including enzymes for the regulation of intracellular substrate pools, membrane receptors for LH, or receptor proteins for lipoproteins, a major extracellular source of substrate.     

Control of endometrial oxytocin receptor and uterine response to oxytocin by progesterone and oestradiol in the ewe

The effects of administration of progesterone and oestradiol on ovine endometrial oxytocin receptor concentrations and plasma concentrations of 13,14-dihydro-15-keto prostaglandin F-2 alpha (PGFM) after oxytocin treatment were determined in ovariectomized ewes. Ewes received progestagen pre-treatment, progesterone and/or oestradiol in 11 different treatment schedules. Progestagen pre-treatment decreased oxytocin receptor concentrations in endometrium from ewes treated subsequently with either progesterone for 5 days or progesterone for 5 days plus oestradiol on Days 4 and 5 of progesterone treatment. Oestradiol increased endometrial oxytocin receptor concentrations when administered on Days 4 and 5 of 5 days progesterone treatment. Progestagen pre-treatment followed by progesterone treatment for 12 days caused a large increase in oxytocin receptors and no further increase occurred when ewes were given oestradiol on Days 11 and 12, or when progesterone was withdrawn on Days 11 and 12, or these two treatments were combined. Oxytocin administration caused an increase in plasma PGFM concentrations in ewes which did not receive progestagen pre-treatment, and subsequently received progesterone treatment for 5 days and oestradiol treatment on Days 4 and 5 of progesterone treatment. Similarly treated ewes which received progestagen pre-treatment did not respond to oxytocin. Oxytocin administration also increased plasma PGFM concentrations in ewes which received progestagen pre-treatment followed by progesterone treatment for 12 days, progesterone treatment for 12 days plus oestradiol on Day 11 and 12 of progesterone treatment, progesterone withdrawal on Day 11 and 12, or progesterone withdrawal and oestradiol treatment combined. The results indicate that (1) progesterone pre-treatment affects oxytocin receptor concentrations in the endometrium and uterine responsiveness to oxytocin and (2) progesterone treatment alone for 12 days after a treatment which mimics a previous luteal phase and oestrus is sufficient to induce oxytocin receptors and increase oxytocin-induced PGF release. These results emphasize the importance of progesterone and provide information which can be used to form an hypothesis for control of luteolysis and oestrous cycle length in the ewe.     

Angiogenesis as a prognostic factor in invasive carcinoma of the uterine cervix

The aim of the study was to evaluate angiogenesis as an independent prognostic factor and to determine the correlation between the angiogenic index (AI) and histologic grade of the neoplastic process in patients operated on for invasive carcinoma of the uterine cervix. Angiogenesis was assessed with immunohistochemical technique using a monoclonal antibody against human factor VIII--(F8/86 M0616, DAKO, Denmark). A positive correlation was revealed between the intensification of angiogenesis and the incidence of lymph node involvement and survival rate.     

Prolactin response to TRH in insulin-dependent diabetes mellitus

17 obese women were examined, 8 of which were diabetic and 9 affected only by essential obesity. These patients, all of whom had become obese during adult life and 8 control subjects were tested for IRI, GH and PRL levels in basal conditions and after infusion of TRH. In the obese and diabetic women fasting GH values were normal while IRI levels were higher than those of the control subjects. In all cases neither IRI nor GH variations during TRH stimulation test. There was no difference in the plasma levels of PRL between the 3 groups when examined in basal conditions. After TRH the hormone increased considerably in all the subjects. In the obese and diabetic obese women the incremental area did not present different values from those observed in the control subjects. In conclusion in insulin-independent diabetes, as in essential obesity, the pharmacological stimulus did not show any evident alteration of the specific hypofisary receptorial system that regulates the secretion of PRL and GH.     

Variability in the response of the rabbit uterus to progesterone as influenced by prolactin

Ovariectomized rabbits from different breeders were treated at different times of the year with prolactin alone or with progesterone and the production of uteroglobin by the uterus was studied. There were seasonal, strain and dose variables in the uterine response to prolactin and progesterone. Treatment with prolactin (at 1 mg/day) plus progesterone generally induced higher levels of uteroglobin production than did treatment with progesterone alone. The differences were greatest in the winter for Tennessee animals and in the spring for animals from the New Mexico and North Carolina colonies. Ovariectomy produced a decrease (P less than 0.01) in the concentration of cytosolic oestrogen and progesterone receptors, and prolactin treatment restored the concentration to oestrous control values. However, there were no seasonally dependent changes in the concentration of the receptors for any of the treatment groups. Increased doses of prolactin (2 mg/day) induced high levels of uteroglobin production and new proteins to appear in uterine secretions of long-term ovariectomized rabbits but much lower levels (10-11%) when given to pregnant does. Additional ovulations were also noted plus adverse effects on the embryos.     

Effect of progesterone on the contractile response of isolated pulmonary artery in rabbits.

The purpose of this study was to assess the direct effect of progesterone on rabbit pulmonary arteries and to examine the mechanism of its action. Rings of pulmonary artery from male rabbits were suspended in organ baths containing Krebs solution, and isometric tension was measured. The response to progesterone was investigated in arterial rings contracted with noradrenaline (NA), KCl, and CaCl2. The effects of endothelium, nitric oxide (NO), prostaglandins, cyclic GMP (cGMP), and the adrenergic beta-receptor on progesterone-induced relaxation were also assessed. Progesterone inhibited the vasocontractivity to NA, KCl, and CaCl2, and relaxed rabbit pulmonary artery. The relaxing response of progesterone in pulmonary artery was significantly reduced by removal of endothelium, inhibitors of nitric oxide synthase and guanylate cyclase, but not by prostaglandin synthase inhibitor and blockage of the adrenergic beta-receptor. In Ca2+-free (0.1 mM EGTA) Krebs solution, progesterone inhibited NA-induced contraction that was intracellular Ca2+-dependent, but didn't affect the contraction of extracellular Ca2+-dependent component. Our results suggest that progesterone induces relaxation of isolated rabbit pulmonary arteries partially via NO and cGMP. Progesterone may also inhibit Ca2+ influx through potential-dependent calcium channels (PDCs) and Ca2+ release from intracellular stores.     

Prolactin response to synthetic TRF in pregnant ewes.

The prolactin secretion response to TRF was similar at all stages of pregnancy (Days 40, 66, 102 and term).     

Prolactin response to stress in neonatally estrogenized male rats

Male Wistar rats were injected either 500 micrograms of estradiol benzoate or olive oil on their first day of life. Blood samples were obtained from the adult by decapitation, by decapitation after 15 min of restraint, by decapitation 10 min after a 5 min period of ether exposure or by jugular venipuncture after 60 s of ether exposure. Prolactin (PRL) plasma levels were measured by RIA. The PRL levels in samples obtained by decapitation were similar to control and estrogenized groups. A similar response to restraint was also found in both groups. Sixty s of exposure to ether stress stimulates PRL secretion only in the estrogenized males, this effect being blocked by treatment with Normifensine (5 mg/kg two hours prior to blood sampling). These results suggested that estrogenized male rats show greater sensitivity to acute ether stress than the controls, and that changes in the dopaminergic system could be involved in this response.     

Variability in gonadotrophin preparations as a factor in the superovulatory response

Much of the variability in superovulatory response has been attributed to variation in ovarian response of individual animals. Alternatively, differences in the relative abundance of FSH and LH activity in gonadotrophin preparations may contribute to superovulatory variation. This report presents evidence for variability in LH and FSH activity among equine chorionic gonadotrophin, porcine FSH and human menopausal gonadotrophins. Lower ratios of $\text{FSH}\text{LH}$ activity appeared to reduce ovulatory success in rats, and addition of PLH to FSH-P reduced superovulation in crossbred cows.     

Oxytocin receptors coupled to uterine contraction in estrogen-dominated rabbits

The present study investigated whether specific [3H]oxytocin binding sites previously demonstrated in estrogen-dominated rabbit uterus have properties expected of physiologic receptors coupled to uterine contraction. Microsomal membranes from estrogen-dominated rabbit uterus were found to contain high-affinity specific oxytocin binding sites with Kd = 2-3 nM. These sites were predominantly myometrial in locus. Specific oxytocin binding exhibited a pH optimum between 7.5 and 8.0. Mg2+ or Mn2+ was necessary for maximal specific [3H]oxytocin binding; in contrast, Ca2+ at submillimolar concentrations inhibited specific binding. Oxytocin binding sites were not detectable in microsomal membranes isolated from progesterone-dominated rabbit uterus. Relative binding and uterotonic activities of 10 synthetic neurohypophyseal hormone analogues were determined in estrogen-dominated rabbit uterus. A qualitative correlation was observed between binding and uterotonic responses. Angiotensin II and insulin did not compete with [3H]oxytocin for uterine binding sites. It is concluded that the specific high affinity [3H]oxytocin binding sites demonstrated in estrogen-dominated rabbit uterus have the selectivity for neurohypophyseal hormone analogues expected for physiologic receptors coupled to uterine contraction.     

Prolactin response to sulpiride in non insulin dependent diabetes mellitus

Blood glucose, insulin and prolactin concentrations were determined before and after sulpiride injection (50 mg i.m.) in 20 non-insulin-dependent diabetic patients (10 with retinopathy and 10 without evidence of retinal damage) and 10 subjects with normal glucose tolerance. Prolactin response to sulpiride was significantly higher in diabetics than in controls (at 20 min., p less than 0.01; at 30 and 60 min., p less than 0.005; at 90 min., p less than 0.01; at 120 min., p less than 0.05). The sulpiride induced hyperprolactinemia did not influence blood glucose and plasma insulin levels in controls as well as in diabetic patients. Prolactin response to sulpiride was the same in diabetics with and in those without retinal changes. We conclude that acute hyperprolactinemia seems to have no influence on glucose homeostasis in normal and non insulin-dependent diabetic subjects.