ACTH treatment disrupts ovarian IGF-I and steroid hormone production

Hyper-adrenal activity and increased glucocorticoid hormone release are associated with disruptions in reproductive function and adverse effects on the ovary. The aim of this investigation was to determine whether elevated glucocorticoid hormone levels can influence ovarian IGF-I synthesis and action in vivo. To elevate endogenous glucocorticoid levels, gilts were treated with ACTH during the luteal phase of the oestrous cycle (days 9-13) while the control group received saline. The gilts were subsequently ovariectomized on either day 14 or day 18 of the oestrous cycle. Follicular fluid (FF) was collected from individual follicles; IGF-I and steroid hormone concentrations were determined by radioimmunoassay, and IGF-binding protein (IGFBP) expression was assessed by Western ligand blotting. Granulosa cells were also recovered and placed in culture to determine IGF-I, progesterone (P(4)) and oestradiol-17beta (E(2)) production levels. The cells were cultured in serum-free medium for 5 days and supplemented with: (a) media alone, (b) IGF-I, (c) FSH and androstenedione (A(4)), or (d) IGF-I with FSH and A(4). The FF from ACTH-treated gilts was characterized by elevated (P<0.05) cortisol levels on day 14 and lower (P<0.05) E(2) values on both day 14 and day 18. Lower (P<0.05) IGF-I concentrations were also measured in the FF of ACTH-treated gilts collected on day 18. This altered hormone profile in FF was associated with impaired IGF-I and steroid hormone synthesis by granulosa cells. IGF-stimulated P(4) production (P<0.01) by cells recovered from ACTH-treated gilts on day 14 was lower (P<0.05). By day 18, IGF-I, P(4) and E(2) production by cells from the ACTH group were all significantly (P<0. 05) lower. These results demonstrate that increased glucocorticoid concentrations can disrupt subsequent ovarian IGF-I synthesis and IGF action in vivo and can, potentially, impair follicle maturation.

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miR-130a-3p regulates steroid hormone synthesis in goat ovarian granulosa cells by targeting the PMEPA1 gene

Theriogenology ◽

10.1016/j.theriogenology.2021.02.012 ◽

2021 ◽

Vol 165 ◽

pp. 92-98

Author(s):

Lu Zhu ◽

Jing Jing ◽

Shuaiqi Qin ◽

Qi Zheng ◽

Jiani Lu ◽

...

Keyword(s):

Granulosa Cells ◽

Steroid Hormone ◽

Hormone Synthesis ◽

Ovarian Granulosa Cells

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Effects of IGF-I infusion on growth and muscle Na(+)-K+ pump concentration in K(+)-deficient rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.5.e810 ◽

1993 ◽

Vol 264 (5) ◽

pp. E810-E815 ◽

Cited By ~ 1

Author(s):

I. Dorup ◽

A. Flyvbjerg

Keyword(s):

Binding Site ◽

Control Group ◽

Recombinant Human Insulin ◽

Ouabain Binding ◽

Muscle Weight ◽

Igf I ◽

Organ Specific ◽

K Deficiency ◽

Edl Muscle

K(+)-deficient rats and control rats were infused for 14 days with vehicle: acetic acid (AcA) or recombinant human insulin-like growth factor-I (IGF-I, 240 micrograms/day) by osmotic minipumps. IGF-I treatment of K(+)-deficient rats did not result in overall growth of carcass or muscles but in marked selective growth of adrenals (+42%) and spleen (+66%). In control rats, IGF-I induced increased body and muscle weight, tibia length, and thymus weight. K+ deficiency was associated with reduced serum IGF-I but unchanged thyroid status. IGF-I treatment of the K(+)-deficient rats restored serum IGF-I and decreased total 3,5,3'-triiodothyronine. In AcA-treated K(+)-deficient rats [3H]ouabain binding site concentration decreased by 63 and 43% in soleus and extensor digitorum longus (EDL) muscle, respectively, compared with the AcA-treated controls. IGF-I had no effect on the [3H]ouabain binding site concentration in the control group, but in K(+)-deficient rats a significant lowering of 26% was observed in EDL. K+ deficiency causes relative organ-specific resistance to the growth-promoting effects of IGF-I, comparable to the effects seen in protein-restricted rats. Reduced circulating IGF-I is not the only cause of the downregulation of Na(+)-K+ pumps in K+ deficiency, and IGF-I treatment of control animals in vivo has no stimulatory effect on the synthesis of Na(+)-K+ pumps.

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GnRH Receptor Expression and Reproductive Function Depend on JUN in GnRH Receptor‒Expressing Cells

Endocrinology ◽

10.1210/en.2017-00844 ◽

2018 ◽

Vol 159 (3) ◽

pp. 1496-1510 ◽

Cited By ~ 7

Author(s):

Carrie R Jonak ◽

Nancy M Lainez ◽

Ulrich Boehm ◽

Djurdjica Coss

Keyword(s):

Target Genes ◽

Reproductive Function ◽

Gnrh Receptor ◽

Receptor Expression ◽

Specific Expression ◽

Α Subunit ◽

Estrous Cycles ◽

Hormone Synthesis

Abstract Gonadotropin-releasing hormone (GnRH) from the hypothalamus regulates synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gonadotropes. LH and FSH are heterodimers composed of a common α-subunit and unique β-subunits, which provide biological specificity and are limiting components of mature hormone synthesis. Gonadotrope cells respond to GnRH via specific expression of the GnRH receptor (Gnrhr). GnRH induces the expression of gonadotropin genes and of the Gnrhr by activation of specific transcription factors. The JUN (c-Jun) transcription factor binds to AP-1 sites in the promoters of target genes and mediates induction of the FSHβ gene and of the Gnrhr in gonadotrope-derived cell lines. To analyze the role of JUN in reproductive function in vivo, we generated a mouse model that lacks JUN specifically in GnRH receptor‒expressing cells (conditional JUN knockout; JUN-cKO). JUN-cKO mice displayed profound reproductive anomalies such as reduced LH levels resulting in lower gonadal steroid levels, longer estrous cycles in females, and diminished sperm numbers in males. Unexpectedly, FSH levels were unchanged in these animals, whereas Gnrhr expression in the pituitary was reduced. Steroidogenic enzyme expression was reduced in the gonads of JUN-cKO mice, likely as a consequence of reduced LH levels. GnRH receptor‒driven Cre activity was detected in the hypothalamus but not in the GnRH neuron. Female, but not male, JUN-cKO mice exhibited reduced GnRH expression. Taken together, our results demonstrate that GnRH receptor‒expression levels depend on JUN and are critical for reproductive function.

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252 EFFECT OF SUPERSTIMULATORY TREATMENT TO DONOR COWS IN OXYGEN CONSUMPTION OF MATURED OOCYTES

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab252 ◽

2013 ◽

Vol 25 (1) ◽

pp. 273

Author(s):

K. Imai ◽

S. Sugimura ◽

M. Ohtake ◽

Y. Aikawa ◽

Y. Inaba ◽

...

Keyword(s):

Oxygen Consumption ◽

Prostaglandin F2α ◽

Gonadotropin Releasing Hormone ◽

Oestrous Cycle ◽

Control Group ◽

Releasing Hormone ◽

And Control ◽

Bovine Oocytes

We previously reported that follicular wave synchronization and follicular growth treatment (FGT) before ovum pick-up (OPU) were effective in improving oocyte competence, which was associated with an increase in related embryos obtained by somatic cell nuclear transfer (Sugimura et al. 2012 Cell. Reprogram. 14, 29–37). However, oxygen consumption in oocytes remained unknown. The present study was designed to examine the differences in oxygen consumption between bovine oocytes obtained by OPU with or without FGT after in vitro maturation. Holstein dry cows (n = 8) were reared under the same feeding and environmental conditions. Two OPU sessions were conducted in each cow to collect immature oocytes, as described by Sugimura et al. (2012). The first OPU session (OPU group) was performed in cows on arbitrary days of the oestrous cycle, using a 7.5-MHz linear transducer with the needle connected to an ultrasound scanner. Follicles larger than 8 mm in diameter were then aspirated and a controlled internal drug release device (CIDR) was inserted on Day 5 (the day of the first OPU session = Day 0). Then 30 Armour units (AU) of FSH (Antrin, Kyoritsu Seiyaku, Tokyo, Japan) was administrated to cows twice a day from Day 7 to 10 in decreasing doses (6, 6, 4, 4, 3, 3, 2, 2 AU day–1). Cloprostenol (prostaglandin F2α; 0.75 mg) was administered in the morning of Day 9. The second OPU session (FGT-OPU group) was performed 48 h after prostaglandin F2α administration (Day 11), and only follicles larger than 5 mm in diameter were aspirated. The CIDR was removed from the cows just before OPU. Collected cumulus–oocyte complexes in the OPU and FGT-OPU groups were matured in vitro as described by Imai et al. [2006 J. Reprod. Dev. 52(Suppl.), S19–S29]. To collect in vivo-matured oocytes (control group), the CIDR was inserted into the cows on arbitrary days of the oestrous cycle (= Day 0), and oestradiol benzoate (0.8 mg) was administered on Day 1. The cows received the FGT treatment (as described above) from Day 6 to 10; however, the CIDR was removed in the evening of Day 8. Buserelin (gonadotropin-releasing hormone; 200 µg) was then administrated in the morning of Day 10, and OPU was performed at 24 h after gonadotropin-releasing hormone administration (Day 11). Oxygen consumption of matured oocytes was measured noninvasively with a scanning electron microscopy system (HV-405SP; Hokuto Denko Co., Tokyo, Japan). Data were analysed by ANOVA followed by a Tukey-Kramer test. There was no difference in the mean oxygen consumption between the FGT-OPU group (0.34 ± 0.02 × 10–14 mol–1, mean ± SEM) and control group (0.40 ± 0.01 × 10–14 mol–1). However, oxygen consumption in the FGT-OPU and control groups was significantly lower (P < 0.01) than that in the OPU group (0.50 ± 0.02 × 10–14 mol–1). These results revealed significantly lower oxygen consumption in OPU-derived in vitro-matured bovine oocytes after FGT treatment compared with those obtained without FGT treatment. Oxygen consumption of oocytes obtained from FGT-OPU was similar to that of in vivo-matured oocytes, which may reflect their cytoplasmic maturation status with high developmental competence.

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Identification of androgen receptor phosphorylation in the primate ovary in vivo

Reproduction ◽

10.1530/rep-10-0140 ◽

2010 ◽

Vol 140 (1) ◽

pp. 93-104 ◽

Cited By ~ 11

Author(s):

Iain J McEwan ◽

Dagmara McGuinness ◽

Colin W Hay ◽

Robert P Millar ◽

Philippa T K Saunders ◽

...

Keyword(s):

Endothelial Cells ◽

Androgen Receptor ◽

Granulosa Cells ◽

Gnrh Antagonist ◽

Follicular Phase ◽

Surface Epithelium ◽

Control Group ◽

Target Tissue ◽

Receptor Phosphorylation

The androgen receptor (AR) is a member of the nuclear receptor superfamily, and is important for both male and female reproductive health. The receptor is a target for a number of post-translational modifications including phosphorylation, which has been intensively studied in vitro. However, little is known about the phosphorylation status of the receptor in target tissues in vivo. The common marmoset is a useful model for studying human reproductive functions, and comparison of the AR primary sequence from this primate shows high conservation of serines known to be phosphorylated in the human receptor and corresponding flanking amino acids. We have used a panel of phosphospecific antibodies to study AR phosphorylation in the marmoset ovary throughout the follicular phase and after treatment with GNRH antagonist or testosterone propionate. In normal follicular phase ovaries, total AR (both phosphorylated and non-phosphorylated forms) immunopositive staining was observed in several cell types including granulosa cells of developing follicles, theca cells and endothelial cells lining blood vessels. Receptor phosphorylation at serines 81, 308, and 650 was detected primarily in the granulosa cells of developing follicles, surface epithelium, and vessel endothelial cells. Testosterone treatment lead to a modest increase in AR staining in all stages of follicle studied, while GNRH antagonist had no effect. Neither treatment significantly altered the pattern of phosphorylation compared to the control group. These results demonstrate that phosphorylation of the AR occurs, at a subset of serine residues, in a reproductive target tissue in vivo, which appears refractory to hormonal manipulations.

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Relative effects of activin and inhibin on steroid hormone synthesis in primate granulosa cells

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.75.6.1556 ◽

1992 ◽

Vol 75 (6) ◽

pp. 1556-1561 ◽

Cited By ~ 19

Author(s):

F. Miro

Keyword(s):

Granulosa Cells ◽

Steroid Hormone ◽

Hormone Synthesis

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In vitro effect of dehydroepiandrosterone sulfate on steroid receptors, aromatase, cyclooxygenase-2 expression, and steroid hormone production in preovulatory human granulosa cells

Fertility and Sterility ◽

10.1016/j.fertnstert.2007.01.008 ◽

2007 ◽

Vol 88 (4) ◽

pp. 1135-1142 ◽

Cited By ~ 5

Author(s):

Khalid ELBeltagy ◽

Ken-ichi Honda ◽

Koji Ozaki ◽

Takuya Misugi ◽

Osamu Tokuyama ◽

...

Keyword(s):

Granulosa Cells ◽

Steroid Receptors ◽

Steroid Hormone ◽

Dehydroepiandrosterone Sulfate ◽

Cyclooxygenase 2 ◽

Hormone Production ◽

Human Granulosa Cells ◽

Vitro Effect

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Granulosa cells of the cumulus oophorus are different from mural granulosa cells in their response to gonadotrophins and IGF-I

Journal of Endocrinology ◽

10.1677/joe.0.1700565 ◽

2001 ◽

Vol 170 (3) ◽

pp. 565-573 ◽

Cited By ~ 23

Author(s):

F Khamsi ◽

S Roberge

Keyword(s):

Granulosa Cells ◽

Cumulus Cells ◽

Saline Control ◽

Cell Replication ◽

Progesterone Secretion ◽

Igf I ◽

Negative Effect ◽

Positive Effect

There are two types of granulosa cells: those which surround the oocyte are cumulus cells (CC) and those which surround the antrum are mural granulosa cells (MGC). These cells are under the influence of several hormones and growth factors, the most important of which are gonadotrophins and IGF-I. In this article, we report novel observations on the differences between these two types of granulosa cells and their interaction with gonadotrophins and IGF-I. We were able to conduct physiological studies on the role of IGF-I by using an analogue of IGF-I which does not bind to IGF-I-binding proteins (LR3-IGF-I). Immature rats received saline, equine chorionic gonadotrophin (eCG), LR3-IGF-I or eCG plus LR3-IGF-I by infusion using a pump from 24-29 days of age. The rats were killed and the ovaries removed. Surface follicles were punctured and MGC and oocyte cumulus complexes were removed. These were cultured in saline (control) and in three different doses of FSH. Cell replication was assessed by 3H-thymidine incorporation and differentiation was evaluated by the measurement of progesterone secretion. It was noted that CC replicated ten times more than MGC. Similarly, progesterone secretion by CC was six times more than by MGC. In vivo exposure to gonadotrophins (eCG) positively influenced in vitro treatment with FSH in both cell types. This phenomenon was observed in both cell replication and progesterone secretion. The IGF-I analogue had a positive effect on cell replication of MGC but a negative effect on the cell replication of CC. With respect to progesterone secretion, the IGF-I analogue had a negative effect on CC but a positive effect on MGC. In conclusion, CC behaved differently from MGC in response to gonadotrophins and the IGF-I analogue. IGF-I and FSH acted additively, synergistically or antagonistically in different circumstances.

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Demonstration of in vivo mammogenic and lactogenic effects of recombinant ovine placental lactogen and mammogenic effect of recombinant ovine GH in ewes during artificial induction of lactation

Journal of Endocrinology ◽

10.1677/joe.0.1600365 ◽

1999 ◽

Vol 160 (3) ◽

pp. 365-377 ◽

Cited By ~ 19

Author(s):

G Kann ◽

A Delobelle-Deroide ◽

L Belair ◽

A Gertler ◽

J Djiane

Keyword(s):

Plasma Levels ◽

Placental Lactogen ◽

Mammary Tissue ◽

Control Group ◽

Dependent Manner ◽

Exogenous Hormone ◽

Daily Group ◽

Igf I ◽

Beta Casein

The present study demonstrates that ovine placental lactogen (oPL) (ovine chorionic somatotrophin) may have an important role in the mammogenesis and/or lactogenesis of the ewe. Its effects were compared with that already described for ovine growth hormone (oGH). In the first experiment, 40 nulliparous ewes were induced to lactate by means of a 7 day (days 1-7) oestro-progestative treatment (E2+P4). The ewes from Group 1 (n=12) received no further treatment, while those of the other groups received either recombinant oGH (roGH, 28 micrograms/kg, i.m., twice daily, Group 2, n=12) or recombinant oPL (roPL, 79 micrograms/kg, i.m., twice daily, Group 3, n=12) from day 11 to 20. All ewes received 25 mg hydrocortisone acetate (HC) twice daily on days 18-20. Control Group 00 (n=2) received no steroid treatment at all, and the control Group 0 (n=2) received only the E2+P4 treatment. Thirteen ewes (three from each experimental group and the two of each control group) were slaughtered at the end of hormone treatments (day 21) before any milking stimulus. The 27 remaining ewes from Groups 1-3 were machine-milked and milk yields recorded daily from day 21 to 76. The E2+P4 treatment enhanced the plasma levels of oPRL, oGH and IGF-I between days 1 and 7 by 1.5, 2. 3 and 2.6 times respectively (P=0.002); roGH treatment induced a highly significant enhancement of IGF-I plasma levels from day 11 to 20, whereas a similar effect appeared for roPL-treated ewes only from day 17 to 20 (P<0.01). Eight weeks after the last exogenous hormone injections, milk yields of both roGH- and roPL-treated groups progressively rose to twice that of unsupplemented groups (P<0.001). The mammary DNA content on day 21 was higher for animals which received either oGH or oPL but, due to individual variations in so few samples (n=3), this difference was not significant. No beta-casein was measured in mammary tissue from control ewes, whereas steroid-treated ewes (E2+P4+HC) had higher casein concentrations regardless of subsequent hormonal treatment on days 11-20 (P<0.001). beta-Casein concentrations in mammary parenchyma of roGH-treated ewes did not differ from that of ewes which received only E2+P4+HC; roPL supplementation clearly enhanced expression of beta-casein (P<0.001). IGF-I stimulation by either roGH or roPL was more precisely examined during a second experiment, in which two twice-daily i.m. doses (58 or 116 micrograms/kg) of either roGH or roPL were administered to four groups of six ewes that were E2+P4 treated as those of Experiment 1. A control group (n=6) received no exogenous hormone from day 11 to 13. On day 13, hourly blood samples were taken from all ewes over 11 h. Both doses of roGH significantly stimulated IGF-I in a dose-dependent manner. The 58 micrograms/kg dose of roPL did not significantly stimulate IGF-I, but although being somewhat less efficient than the 58 micrograms/kg dose of roGH, the 116 micrograms/kg dose of roPL significantly stimulated IGF-I secretion (P<0. 001). These results suggest that mammogenesis and/or lactogenesis in the ewe is in part controlled by somatotrophic hormones such as oGH and oPL and that IGF-I could be one of the mediators of these hormones.

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