Kisspeptin as autocrine/paracrine regulator of human ovarian cell functions: Possible interrelationships with FSH and its receptor

The present study aims to examine the role of kisspeptin (KP), FSH, and its receptor (FSHR), and their interrelationships in the control of basic human ovarian granulosa cells functions. We investigated: (1) the ability of granulosa cells to produce KP and FSHR, (2) the role of KP in the control of ovarian functions, and (3) the ability of KP to affect FSHR and to modify the FSH action on ovarian functions. The effects of KP alone (0, 10 and 100 ng/mL); or of KP (10 and 100 ng/mL) in combination with FSH (10 ng/mL) on cultured human granulosa cells were assessed. Viability, markers of proliferation (PCNA and cyclin B1) and apoptosis (bax and caspase 3), as well as accumulation of KP, FSHR, and steroid hormones, IGF-I, oxytocin (OT), and prostaglandin E2 (PGE2) release were analyzed by the Trypan blue exclusion test, quantitative immunocytochemistry, and ELISA. KP given at a low dose (10 ng/mL) stimulated viability, proliferation, inhibited apoptosis, promoted the release of progesterone (P4), estradiol (E2), IGF-I, OT, and PGE2, the accumulation of FSHR, but not testosterone (T) release. KP given at a high dose (100 ng/mL) had the opposite, inhibitory effect. FSH stimulated cell viability, proliferation and inhibited apoptosis, promoted P4, T, E2, IGF-I, and OT, but not PGE2 release. Furthermore, KP at a low dose promoted the stimulatory effect of FSH on viability, proliferation, P4, E2, and OT release, promoted its inhibitory action on apoptosis, but did not modify its action on T, IGF-I, and PGE2 output. KP at a high dose prevented and inverted FSH action. These results suggest an intra-ovarian production and a functional interrelationship between KP and FSH/FSHR in direct regulation of basic ovarian cell functions (viability, proliferation, apoptosis, and hormones release). The capability of KP to stimulate FSHR, the ability of FSH to promote ovarian functions, as well as the similarity of KP (10 ng/mL) and FSH action on granulosa cells’ viability, proliferation, apoptosis, steroid hormones, IGF-I, OT, and PGE2 release, suggest that FSH influence these cells could be mediated by KP. Moreover, the capability of KP (100 ng/mL) to decrease FSHR accumulation, basal and FSH-induced ovarian parameters, suggest that KP can suppress some ovarian granulosa cell functions via down-regulation of FSHR. These observations propose the existence of the FSH-KP axis up-regulating human ovarian cell functions.     

The effect of follicle-stimulating hormone on follicular development, granulosa cell apoptosis and steroidogenesis and its mediation by insulin-like growth factor-I in the goat ovary

The effect of FSH on goat follicular development, granulosa cell apoptosis and steroidogenesis and its mediation by insulin-like growth factor (IGF)-I were studied through both in vivo and in vitro experiments. The FSH treatment was begun on Day 9 after estrus and consisted of injections twice a day for 3 days in decreasing doses (7.5–7.5–5.0–5.0–2.5–2.5 mg). Does in both treatment and control groups were slaughtered for ovaries on Day 12. Granulosa cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Expression of IGF-I and IGF-II mRNA was determined by RT–PCR, while concentrations of progesterone (P4), estradiol (E2), IGF-I and IGF-II were measured by radioimmunoassay (RIA). Following parameters increased significantly (P<0.05) after the FSH treatment: follicle number (5.0±1.5 versus 9.0±2.0 per ovary), the level of E2 (0.1±0.1 ng/ml versus 0.7±0.2 ng/ml), the E2/P4 ratio (0.7±0.4 versus 4.7±3.0) and the concentrations of IGF-I (0.5±0.2 ng/ml versus 119.4±15.1 ng/ml) and IGF-II (0.12±0.03 ng/ml versus 40.9±18.7 ng/ml) in follicular fluid of the medium sized (3–5 mm) follicles and in the ovarian cortex the relative quantity of IGF-I mRNA (0.37±0.17 versus 0.90±0.12 Max OD). In contrast, the ratio of apoptotic granulosa cells in these follicles was reduced significantly (0.53±0.1 versus 0.10±0.01, P<0.05). In large (>5 mm) follicles, however, only the follicle number (2.3±0.7 versus 7.0±1.5 per ovary) and the level of IGF-I (38.4±11.0 ng/ml versus 87.3±13.9 ng/ml) increased significantly (P<0.05), whereas other values did not change. In vitro culture of granulosa cells showed that FSH significantly (P<0.05) enhanced IGF-I production (12.7±2.1 ng/ml versus 26.±21.9 ng/ml) by these cells, and both FSH and IGF-I reduced the ratios of apoptotic cells (from 0.7±0.07 to 0.3±0.1 and 0.2±0.04, respectively) and the effect was additive when both were used together. H89, the PKA pathway inhibitor, blocked the effect of FSH on granulosa cell apoptosis and IGF-I production in vitro. These results indicated that FSH mainly enhanced the development of medium sized follicles in the goat by suppressing the apoptosis of granulosa cells via increasing production of IGF-I and steroids, possibly through the PKA pathway.     

Some endocrine traits of transgenic rabbits. II. Changes in hormone secretion and response of isolated ovarian tissue to FSH and ghrelin

In the present in vitro experiments we examined FSH- and ghrelin-induced changes in ovarian hormone secretion by transgenic rabbits. Fragments of ovaries isolated from adult transgenic (carrying mammary gland-specific mWAP-hFVIII gene) and non-transgenic rabbits from the same litter were cultured with and without FSH or ghrelin (both at 0, 1, 10 or 100 ng/ml medium). The secretion of progesterone (P4), estradiol (E2) and insulin-like growth factor I (IGF-I) was assessed by RIA. It was observed that ovaries isolated from transgenic rabbits secreted much less P4, E2 and IGF-I than the ovaries of non-transgenic animals. In control animals FSH reduced E2 (at doses 1-100 ng/ml medium) and IGF-I (at 1-100 ng/ml), but not P4 secretion, whereas ghrelin promoted P4 (at 1 ng/ml) and IGF-I (at 100 ng/ml), but not E2 output. In transgenic animals, the effects were reversed: FSH had a stimulatory effect on E2 (at 100 ng/ml) and ghrelin had an inhibitory effect on P4 (at 10 ng/ml). No differences in the pattern of influence of FSH on P4 and IGF-I and of ghrelin on E2 and IGF-I were found between control and transgenic animals. The present observations suggest that 1) both FSH and ghrelin are involved in rabbit ovarian hormone secretion, 2) transgenesis in rabbits is associated with a reduction in ovarian secretory activity, and 3) transgenesis can affect the response of ovarian cells to hormonal regulators.     

Effect of gonadotropin-releasing hormone,stage of sexual maturation and 6-methoxybenzoxazolinone on plasma gonadotropins,ovarian development and uterine weight in prepuberal gilts

Two experiments were conducted with prepuberal gilts at 60, 120 and 160 days of age to a) determine the effect of 6-methoxybenzoxazolinone 6-MBOA) on reproductive plasma hormone concentrations and organ development, and b) determine how plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations before and after injection of gonadotropin-releasing hormone (GnRH) or 6-MBOA varied in relation to ovarian development. In Exp. 1, 12 gilts were used in a 4×4 Latin square design. Four gilts/age group were injected once with: 1) vehicle, 2.5% propylene glycol in 50% ethanol, 2) 2 μg of GnRH/kg body weight (BW), 3) 0.2 mg of 6-MBOA/kg BW, and 4) 2 mg of 6-MBOA/kg BW on four successive days in random order. Blood was collected via indwelling vena cava catheters. Injection of GnRH into gilts increased plasma FSH and LH at each age compared with vehicle (P<0.05). Hormone profiles for FSH and LH differed among age groups (P<0.01), but area under curves did not differ significantly among age groups. Injection of 6-MBOA did not significantly affect plasma FSH and LH. Plasma FSH and LH before the GnRH injection or on days when GnRH was not injected were greater at 60 than at 120 and 160 days (FSH, 128 vs 54 and 42 ng/ml; LH, 0.38 vs 0.16 and 0.13 ng/ml for 60, 120 and 160 days, respectively (P<0.05). In Exp. 2, vehicle, 0.2 or 2 mg of 6-MBOA/kg BW were injected once daily for 7 days in 19 gilts. Injections of 6-MBOA had no detectable effects on gonadotropin secretion, ovarian development or uterine weight. Between 60 and 120 days of age, vesicular follicles developed, ovarian weight increased 20-fold, and uterine weight increased 10-fold (P<0.05); basal concentrations of plasma FSH and LH decreased three- and twofold, respectively.     

Insulin-like growth factor-I feedback regulation of growth hormone and luteinizing hormone secretion in the pig: evidence for a pituitary site of action

Three experiments (EXP) were conducted to determine the role of insulin-like growth factor-I (IGF-I) in the control of growth hormone (GH) and LH secretion. In EXP I, prepuberal gilts, 65 ± 6 kg body weight and 140 days of age received intracerebroventricular (ICV) injections of saline (n = 4), 25 μg (n = 4) or 75 μg (n = 4) IGF-I and jugular blood samples were collected. In EXP II, anterior pituitary cells in culture collected from 150-day-old prepuberal gilts (n = 6) were challenged with 0.1, 10 or 1000 nM [Ala15]-h growth hormone-releasing hormone-(1-29)NH2 (GHRH), or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 1000 nM GHRH. Secreted GH was measured at 4 and 24 h after treatment. In EXP III, anterior pituitary cells in culture collected from 150-day-old barrows (n = 5) were challenged with 10, 100 or 1000 nM gonadotropin-releasing hormone (GnRH) or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 100 nM GnRH. Secreted LH was measured at 4 h after treatment. In EXP I, serum GH and LH concentrations were unaffected by ICV IGF-I treatment. In EXP II, relative to control all doses of GHRH increased (P < 0.01) GH secretion. Only 1, 10, 30 nM IGF-I enhanced (P < 0.02) basal GH secretion at 4 h, whereas by 24 h all doses except for 30 nM IGF-I suppressed (P < 0.02) basal GH secretion compared to control wells. All doses of IGF-I in combination with 1000 nM GHRH increased (P < 0.04) the GH response to GHRH compared to GHRH alone at 4 h, whereas by 24 h all doses of IGF-I suppressed (P < 0.04) the GH response to GHRH. In EXP III, all doses of IGF-I increased (P < 0.01) basal LH levels while the LH response to GnRH was unaffected by IGF-I (P > 0.1). In conclusion, under these experimental conditions the results suggest that the pituitary is the putative site for IGF-I modulation of GH and LH secretion. Further examination of the role of IGF-I on GH and LH secretion is needed to understand the inhibitory and stimulatory action of IGF-I on GH and LH secretion.     

Changes in circulating levels of immunoreactive follicle stimulating hormone, luteinizing hormone, and testosterone during sexual development in the rhesus monkey, Macaca mulatta

Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH.     

Implication of microtubules and microfilaments in the response of the ovarian adenylate cyclase-cyclic AMP system to gonadotropins and prostaglandin E2.

Addition of anti-actin serum or cytochalasin B (3 μg/ml) to the medium abolished the stimulatory effect of LH and of choleragen, and inhibited the action of FSH, but not of PGE₂, on cyclic AMP production in cultured rat Graafian follicles. Colchicine and anti-sera to BSA, tubulin or smooth-muscle myosin, as well as anti-actin serum absorbed with actin, had no effect on the follicular response to LH, but anti-tubulin serum and colchicine inhibited the response to FSH and PGE₂. The inhibitory effect of cytochalasin B on LH-action was fully reversed 24 h after transfer of the follicles to drug-free medium. Neither anti-actin serum nor cytochalasin B had any effect on the binding of ¹²⁵I-hCG by the follicular cell membrane. The results suggest that microfilaments, but not microtubules, are intimately involved in the process of LH- and choleragen-stimulated ovarian adenylate cyclase activity. By contrast, the action of PGE₂ is dependent on microtubule assembly, while the action of FSH seems to depend on both these components of the cytoskeleton.     

Involvement of obestatin,cyclin-dependent kinase and protein kinase C in control of feline ovarian cell viability and hormones release

The aim of our in vitro study was to understand the role of obestatin, cyclin-dependent kinase (CDK) and protein kinase C (PKC) in the control of basic feline ovarian cell functions (viability, ovarian hormones release), as well as the role of protein kinases in mediating the effect of obestatin on these processes. For this purpose, we analyzed the effect of obestatin (0, 10 and 100 ng/mL) alone or in combination with CDK blocker olomoucine (100 ng/mL) or PKC blocker calphostin-c (100 ng/mL) on cultured feline ovarian fragments or granulosa cells. The release of progesterone (P4), testosterone (T) and estradiol (E2) by isolated ovarian follicular fragments were evaluated by ELISA. Granulosa cell viability was analysed using the Trypan blue exclusion test. It was observed that the addition of obestatin alone significantly increased the granulosa cell viability (at dose 100 ng/mL), promoted the release of P4 (at all doses added) and IGF-I (at dose 100 ng/mL) but decreased T (at all doses added). E2 output was below the detection limit in all groups. The addition of either olomoucine or calphostin-c reduced cell viability, P4, T and IGF-I release. Both olomoucine and caplhostin-c inverted the stimulatory effect of obestatin on granulosa cell viability and were able to prevent stimulatory action of obestatin on ovarian cell viability and on hormone and growth factor release and change it to an inhibitory action. These observations show that obestatin can directly regulate (mostly promote) basal feline ovarian cell functions (hormone release and viability). The inhibitory action of CDK and PKC blockers on these functions suggests, that both CDK and PKC can be promoters of ovarian cell viability and steroidogenesis in cats. Furthermore, the ability of both CDK and PKC to prevent olomoucine action demonstrates that obestatin action on the feline ovary could be mediated by these kinases.     

Effect of insulin-like growth factor-I on some quality traits and fertility of cryopreserved ovine semen

The objective was to evaluate the effects of insulin-like growth factor-I (IGF-I) on the quality and fertility of frozen/thawed ovine semen. Five rams (five ejaculates/ram) were used for evaluation of semen parameters. Before cryopreservation, ejaculates were divided into four aliquots and extended with Tris alone or supplemented with human IGF-I (50, 100, or 250 ng/mL). Semen was evaluated immediately after thawing (T0), after 1 h (T1) and 2 h (T2) post-incubation at 37 °C. The percentage of live cells (fluorescence analysis-calcein and ethidium), acrosome integrity (NAR) and motility were analyzed, and hypo-osmotic swelling tests (HOST) were used to evaluate membrane resistance. In addition, AI was performed using 121 ewes to compare the optimal concentration of IGF-I vs. Tris alone on pregnancy rates after laparoscopic insemination. Pregnancy diagnosis was performed by transrectal ultrasonography. After 1 and 2 h post-incubation, in every group, percentage motile sperm, NAR and HOST decreased compared to semen at T0. Motility was higher (P < 0.05) in the IGF-I 100 and IGF-I 250 groups when compared to the IGF-I 50 and Tris groups (76.2 and 74.4% vs. 66.2 and 64.4 percent, respectively) at T0, after 1 h (67 and 63.6% vs. 56.2 and 54.7%) and 2 h post-incubation (58.2 and 55.8% vs. 48 and 47.2%). Furthermore, viability was higher (P < 0.05) in the insulin-like growth factor-I (IGF-I) 100 and IGF-I 250 groups than in the IGF-I 50 and Tris groups (88.7 and 88.3% vs. 76.6 and 77.6%, respectively) at T0. There was no difference (P > 0.05) in NAR or hypo-osmotic swelling tests (HOST) among groups. There were no differences (P > 0.05) in fertility between the IGF-I 100 and Tris groups. In conclusion, IGF-I improved subjective sperm motility and structural integrity of the plasma membrane without a significant effect on 45-day pregnancy rates after laparoscopic insemination of ewes with frozen-thawed semen.     

Effect of recombinant growth hormone on expression of growth hormone receptor, insulin-like growth factor mRNA and serum level of leptin in growing pigs

Growth hormone (GH) plays an important role in regulation of animal growth, metabolism and lactation[1]. Numerous studies have shown that exogenous somatotropin (ST) can increase average daily weight gain, improve feed efficiency, stimulate protein deposition and muscle growth and decrease lipid accretion rate[1]. The original somatomedin hypothesis suggested that the effect of GH on postnatal growth was mediated by insulin-like growth hormone factor 1 (IGF-I) which was thought to be deriv…     

Follicle stimulating hormone secretion and compensatory ovarian hypertrophy in prepubertal ewes

A study was conducted to determine the effect of unilateral ovariectomy (ULO) on follicle stimulating hormone (FSH) secretion and compensatory ovarian hypertrophy in prepubertal ewes. Thirty-three ewe lambs were allotted according to age and weight to a control (C) or ULO group. In the C group, a sham ovariectomy was performed on day 0 and both ovaries were removed on day 7. In the ULO group, one ovary was removed on day 0 and the remaining ovary was removed on day 7. Blood samples were collected from the jugular vein via venipuncture at 0, 6, 12 and 24 hours after the time of sham surgery or ULO (day 0). Subsequent samples were collected daily until day 7, and all samples were assayed for FSH and LH. Unilateral ovariectomy increased (P<0.01) ovarian weight and follicular fluid weight; however, lyophilized ovarian weight was similar for both groups. Within the ULO group, removal of the ovary having the largest follicle(s) did not prevent an increase in ovarian weight or follicular fluid weight of the remaining ovary. Unilateral ovariectomy had no effect on the total number of follicles (1 to 6 mm) per ovary; however, the number of large (5 to 6 mm) follicles per ovary was increased (P<0.05) following ULO. By 12 hours after ULO there was a transient increase (P<0.05) in the circulating concentrations of FSH. Circulating concentrations of luteinizing hormone (LH) were either low or undetectable in these prepubertal ewes and no LH response was observed following ULO. These results indicate that compensatory ovarian hypertrophy in ULO prepubertal ewes is accompanied by a transient rise in circulating FSH concentrations.     

Ghrelin and obestatin can promote human ovarian granulosa cell functions and FSH effects

The aim of the present in-vitro experiments was to examine the direct influence of ghrelin and obestatin on viability, proliferation and progesterone release by human ovarian granulosa cells and their response to FSH administration. Human granulosa cells were cultured in presence of ghrelin or obestatin (both at 0, 1, 10 or 100 ng/ml) alone or in the presence of FSH (10 ng/ml). Cell viability, accumulation of proliferation markers PCNA and cyclin B1 and release of progesterone were analyzed by Trypan blue extrusion test, quantitative immunocytochemistry and ELISA. Ghrelin, obestatin and FSH up-regulated all the measured ovarian cell parameters. Moreover, both ghrelin and obestatin promoted all the stimulatory effects of FSH. The obtained results demonstrate the direct stimulatory action of ghrelin, obestatin and FSH on basic ovarian cell functions, as well as the ability of metabolic hormones to improve FSH action on human ovarian cells.     

Effects of luteinizing hormone and follicle-stimulating hormone and insulin-like growth factor-I on aromatase activity and P450 aromatase gene expression in the ovarian follicles of red seabream,Pagrus major

To clarify the mechanism of estradiol-17beta production in the ovarian follicle of red seabream, in vitro effects of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and insulin-like growth factor (IGF-I) on aromatase activity (conversion of testosterone to estradiol-17beta) and cytochrome P450 aromatase (P450arom) mRNA expression in ovarian fragments of red seabream were investigated. Of the growth factors used in the present study, only IGF-I stimulated both aromatase activity and P450arom gene expression in the ovarian fragments of red seabream. LH from red seabream pituitary, but not FSH, stimulated both aromatase activity and P450arom gene expression. IGF-I slightly enhanced the LH-induced aromatase activity and P450arom gene expression. These data and our previous results indicate that LH, but not FSH, stimulates estradiol-17beta production in the ovarian follicle of red seabream through stimulation of aromatase activity and P450arom gene expression and IGF-I enhances the LH-stimulated P450arom gene expression.     

Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH,LH and PRL levels in patients with polycystic ovarian syndrome

ObjectiveEffects of human chorionic gonadotropin combined with clomiphene on serum E₂, FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed.Methods90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E₂, FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated.ResultsSerum E₂, FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant (P < 0.05). After the treatment, E₂, FSH, LH and PRL levels in the observation group were lower than that in the control group and the difference is statistical significant (P < 0.05). Total effective rate was 64.44% in the control group and 93.33% in the observation group. There were statistically significant difference in clinical curative effects in the two groups (P < 0.05). Different degrees of adverse reactions were found in both groups during treatment, such as nausea, vomiting, anorexia, liver dysfunction. There were 2 cases of nausea, 2 cases of vomiting, 3 cases of anorexia and 1 case of liver dysfunction from the 45 patients in control group. The total incidence of adverse reactions was 17.78% (8/45). There were 1 case of nausea, 1 case of vomiting, 1 case of anorexia and no liver dysfunction from the 45 patients in observation group. The total incidence of adverse reactions was 6.67% (3/45). The total incidence of adverse reactions in the observation group was significantly higher than that in the control group and the difference was not statistically significant (P > 0.05).ConclusionCombined use of human chorionic gonadotropin can significantly reduce serum E₂, FSH, LH and PRL levels, improve clinical curative effects and reduce the incidence of adverse reactions. Human chorionic gonadotropin has high application value on the treatment of polycystic ovary syndrome.     

Chronic alcohol consumption,type 2 diabetes mellitus,insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats

Aims

Alcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats.

Main method

OLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated.

Key findings

Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group.

Significance

These results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels.     

Effects of cadmium and zinc on plasma levels of growth hormone, insulin-like growth factor I, and insulin-like growth factor-binding protein 3

Humans are constantly exposed to cadmium (Cd) as a result of the increase in air pollution and cigaret use. Zinc (Zn), which is an essential element for the metabolism of and the constituent of many enzymes, causes growth retardation in the deficiency status so at present it is often added to the diet without measuring blood levels of this element. We also aimed to observe the effects of both Cd and Zn on the plasma levels of growth hormone (GH), insulin-like growth factor I(IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3) in this study. For this purpose, 27 young Wistar albino male rats were divided into three groups. The first group was given 50 mg/L of CdCl₂, the second group received 500 mg/L of ZnSO₄, and the third group, as a control, received only drinking water for 1 mo. At the end of this period, plasma GH, IGF-I, and IGFBP-3 of the animals were analyzed in the blood obtained. The significance between groups was evaluated with the Mann-Whitney U-test. According to our results, levels of IGF-I and IGFBP-3 in the Cd-administered group were significantly lower than those of controls (p<0.05 and p<0.01 respectively). No statistically significant difference was observed between Zn administered and control groups in terms of all three parameters. These results show that although the addition of Zn to the diet of healthy rats had no effect on the levels of GH, IGF-I, and IGFBP-3, Cd addition lowered the levels of IGF-I and IGFBP-3 but did not change the levels of GH compared to controls.     

Follicle-stimulating hormone promotes the transformation of cholesterol to estrogen in mouse adipose tissue

Follicle-stimulating hormone (FSH) levels increase estrogen biosynthesis in obese menopausal women. Ovariectomized mice and 3T3-L1 cells were used to explore estrogen biosynthesis in the decline of ovarian function. After ovariectomy, lipid deposition, and FSH and estrogen levels changed, and feed intake increased significantly. In mouse adipose tissue, FSH was found to have a role in accelerating lipid deposition via the peroxisome proliferators-activated receptor pathway, and in inducing estrogen biosynthesis via the steroid hormone metabolism pathway. Furthermore, FSH bound to the FSH receptor promoted CREB phosphorylation, which was activated by cAMP-PKA. Moreover, pCREB could up-regulate PPARγ and SREBP2 mRNA levels, resulting in an increased transformation of cholesterol to estrogen. Overall, this study shows that FSH induces fat deposition and promotes the transformation of cholesterol to estrogen through CREB activation by cAMP-PKA in mouse adipose tissue. Our findings provide a new understanding of menopause treatment.