scholarly journals Effect of the metabolic environment at key stages of follicle development in cattle: focus on steroid biosynthesis

2012 ◽  
Vol 44 (9) ◽  
pp. 504-517 ◽  
Author(s):  
S. W. Walsh ◽  
J. P. Mehta ◽  
P. A. McGettigan ◽  
J. A. Browne ◽  
N. Forde ◽  
...  
Keyword(s):  
Luteal Phase ◽  
Ovarian Follicle ◽  
Regulatory Protein ◽  
Follicle Development ◽  
Preovulatory Follicle ◽  
Dominant Follicle ◽  
Beef Heifers ◽  
Steroid Biosynthesis ◽  
Lh Surge ◽  
Lactating Cows

Cellular mechanisms that contribute to low estradiol concentrations produced by the preovulatory ovarian follicle in cattle with a compromised metabolic status are largely unknown. To gain insight into the main metabolic mechanisms affecting preovulatory follicle function, two different animal models were used. Experiment 1 compared Holstein-Friesian nonlactating heifers ( n = 17) and lactating cows ( n = 16) at three stages of preovulatory follicle development: 1) newly selected dominant follicle in the luteal phase (Selection), 2) follicular phase before the LH surge (Differentiation), and 3) preovulatory phase after the LH surge (Luteinization). Experiment 2 compared newly selected dominant follicles in the luteal phase in beef heifers fed a diet of 1.2 times maintenance (M, n = 8) or 0.4 M ( n = 11). Lactating cows and 0.4 M beef heifers had higher concentrations of β-hydroxybutyrate, and lower concentrations of glucose, insulin, and IGF-I compared with dairy heifers and 1.2 M beef heifers, respectively. In lactating cows this altered metabolic environment was associated with reduced dominant follicle estradiol and progesterone synthesis during Differentiation and Luteinization, respectively, and in 0.4 M beef heifers with reduced dominant follicle estradiol synthesis. Using a combination of RNA sequencing, Ingenuity Pathway Analysis, and qRT-PCR validation, we identified several important molecular markers involved in steroid biosynthesis, such as the expression of steroidogenic acute regulatory protein ( STAR) within developing dominant follicles, to be downregulated by the catabolic state. Based on this, we propose that the adverse metabolic environment caused by lactation or nutritional restriction decreases preovulatory follicle function mainly by affecting cholesterol transport into the mitochondria to initiate steroidogenesis.

Defining the gonadotrophin requirement for the selection of a single dominant follicle in cattle

2020 ◽  
Vol 32 (3) ◽  
pp. 322 ◽  
Author(s):  
Jin G. Gong ◽  
Bruce K. Campbell ◽  
Robert Webb
Keyword(s):  
Major Effect ◽  
Follicle Development ◽  
Preovulatory Follicle ◽  
Ultrasound Scanning ◽  
Dominant Follicle ◽  
Initial Exposure ◽  
Preovulatory Follicles ◽  
Gonadotrophin Releasing Hormone ◽  
Follicular Response ◽  
Selection Of

The aim was to define the pattern and physiological concentrations of FSH and LH required for the selection of a single dominant follicle in mono-ovulatory species. A series of five experiments was carried out using gonadotrophin-releasing hormone agonist-induced hypogonadal heifers. Animals were infused with different patterns of either FSH and/or LH followed by an ovulatory dose of human chorionic gonadotrophin. Follicular response was monitored by ultrasound scanning and blood samples were collected to measure concentrations of FSH, LH, oestradiol and progesterone. The main findings were: (1) physiological concentrations of FSH given as a continuous infusion and for an adequate duration, in the presence of basal LH, with or without LH pulses, are capable of inducing a superovulatory response, (2) initial exposure to FSH followed by LH pulses alone stimulate the development of multiple preovulatory follicles, confirming that ovarian follicles are capable of transferring dependence on gonadotrophins from FSH to LH, (3) while LH pulses appear not to have a major effect on the pattern of preovulatory follicle development, adequate LH pulsatile support is required for full oestradiol synthesis and (4) the duration of initial exposure to FSH and the ability to transfer the dependence from FSH to LH are critical for the selection of a single dominant follicle. In conclusion, this experimental series confirms that the duration of initial exposure to FSH and the ability of the selected follicle to transfer its gonadotrophic dependence from FSH to LH are critical for the selection of a single dominant follicle in cattle.

Antifolliculogenic action of progesterone despite hypersecretion of FSH in monkeys

1982 ◽  
Vol 243 (5) ◽  
pp. E387-E397 ◽  
Author(s):  
A. L. Goodman ◽  
G. D. Hodgen
Keyword(s):  
Luteinizing Hormone ◽  
Luteal Phase ◽  
Functional Role ◽  
Follicle Stimulating Hormone ◽  
Dominant Follicle ◽  
Follicle Growth ◽  
Lh Surge ◽  
The Face ◽  
Peripheral Conversion ◽  
Midluteal Phase

To learn how progesterone (P) inhibits follicle growth during the luteal phase, we determined whether P will inhibit follicle growth when follicle-stimulating hormone (FSH) is secreted in large amounts, namely, after luteectomy (CLX) in monkeys with only one ovary. Second, a functional role for 17 alpha-hydroxyprogesterone (17OHP) was examined as a common mediator of the inhibition of folliculogenesis by the dominant follicle and corpus luteum. To accomplish the first goal, nine chronically hemiovarectomized monkeys were lutectomized chronically hemiovariectomized monkeys were luteectomized at midluteal phase. In five monkeys that received no steroid, the next preovulatory luteinizing hormone (LH) surge occurred 14.0 +/- 0.8 days (mean +/- SE) after CLX. In contrast, the next LH surge was delayed in four monkeys implanted for 10 days with Silastic capsules containing P and occurred 25.0 +/- 2.7 days after CLX, i.e., 14.8 +/- 2.7 days after the capsule removal. In both groups, FSH levels increased markedly after CLX to a comparable degree and duration; yet, only a single follicle ovulated in each monkey. To examine a potential inhibitory role for 17OHP, monkeys with two ovaries were luteectomized and received 1) no steroid, 2) 17OHP via Silastic capsules, or 3) P for 10 days after CLX. Progesterone replacement after CLX appeared to maintain 17OHP levels, which showed a transient decrease after CLX alone. As above, P delayed the next LH surge (25.4 +/- 1.3 vs. 15.0 +/- 0.6 days) despite comparable increases in serum FSH after CLX alone. Replacement at two levels of 17OHP did not delay the onset of menses (2-3 days post-CLX) or significantly delay the next LH surge 18.3 +/!- 1.9 or 20.8 +/- 3.4 vs. 15.0 +/- 0.6 days (P greater than 0.2) in monkeys CLX only. Whatever may be the mode of action of P, it appears that it is not mediated by peripheral conversion to 17OHP. These findings demonstrate that P at luteal phase levels can inhibit follicle growth culminating in ovulation even in the face of sustained, elevated levels of endogenous FSH. Because single ovulations occurred despite unambiguous and prolonged increments in serum FSH after CLX, the precise regulation of the ovulatory quota in this primate appears to be accomplished by means other than FSH alone.

scholarly journals Effects of oestradiol and progesterone on secretion of gonadotrophins and health of first wave follicles during the oestrous cycle of beef heifers

Reproduction ◽  
2002 ◽  
pp. 531-541 ◽  
Author(s):  
EJ Austin ◽  
M Mihm ◽  
AC Evans ◽  
JL Ireland ◽  
JJ Ireland ◽  
...  
Keyword(s):  
Growth Factor ◽  
Antral Follicle ◽  
Follicle Development ◽  
Dominant Follicle ◽  
Beef Heifers ◽  
Follicle Diameter ◽  
Oestradiol Benzoate ◽  
Lh Release ◽  
Follicle Selection ◽  
Intravaginal Device

Antral follicle development in cattle is initially FSH dependent and then LH dependent. The aim of the present study was to determine the effects of oestradiol- and progesterone-induced suppression of FSH and LH on growth and differentiation of first wave follicles. Cyclic heifers (n = 45, n = 6-10 per group) received the following i.m. injections or treatments beginning 30 h after oestrus: (i) saline (controls); (ii) 0.75 mg oestradiol benzoate (ODB); (iii) insertion of a progesterone-releasing intravaginal device (PRID) for 42 h (progesterone); (iv) 0.75 mg oestradiol benzoate plus PRID (ODB plus progesterone); (v) 0.75 mg ODB plus injection of 1 mg Ovagen(TM) at 33, 39 and 45 h after onset of oestrus (ODB plus FSH). In Expt 1, follicle development was monitored by ovarian ultrasonography once a day. In Expt 2, heifers were ovariectomized. Emergence of the first follicle wave and dominant follicle selection were delayed in ODB plus progesterone-treated heifers compared with controls. Interval to nadir FSH concentration was shorter in ODB-, progesterone- and ODB plus progesterone-treated heifers compared with controls. Frequency of LH pulses was unaffected in ODB- or ODB plus FSH-treated heifers, decreased in progesterone-treated heifers and further decreased in ODB plus progesterone-treated heifers. Intrafollicular oestradiol concentrations were lower in the largest follicle from ODB plus progesterone-treated heifers compared with control (66 h) heifers, but follicle diameter and concentrations of insulin-like growth factor binding proteins (IGFBPs) and inhibin forms were unaffected. Treatment with ODB decreased follicular oestradiol concentration in smaller follicles in the cohort. It is concluded that growing cohort follicles are uniformly responsive to increased FSH concentration but differentially responsive to suppressed FSH and LH release, which is consistent with an LH-mediated survival advantage of the largest follicle in the cohort before cessation of the growth of remaining follicles in the cohort occurs.

The use of GNRH to control follicular development in cows

1996 ◽  
Vol 1996 ◽  
pp. 95-95
Author(s):  
A.R. Peters ◽  
S.J. Ward ◽  
P.J. Gordon ◽  
G.E. Mann
Keyword(s):  
Dairy Cows ◽  
Present Experiment ◽  
Luteal Phase ◽  
Ovarian Function ◽  
Steroid Hormone ◽  
Follicular Development ◽  
Follicle Development ◽  
Preovulatory Follicle ◽  
Hormone Production ◽  
Gonadotrophin Releasing Hormone

Fertility after prostaglandin (PG) may be compromised by the variability in timing of oestrus and ovulation, which are in turn influenced by the ovarian follicular status at the time of injection. Gonadotrophin-releasing hormone (GnRH) treatment in the luteal phase a few days before PG can reprogramme and thus synchronise preovulatory follicle development (Wolfenson et al., 1994). A second GnRH treatment can then be given after PG, to further improve the synchrony of ovulation (Pursley et al., 1995). The present experiment was carried out to test the effect of this combined GnRH - PG - GnRH regime on ovarian function and steroid hormone production in dairy cows.

scholarly journals 13 EFFECTS OF PRESYNCHRONIZATION WITH A USED CIDR, AND TREATMENT WITH eCG ON FERTILITY IN LACTATING COWS SUBJECTED TO A COSYNCH PROTOCOL

2005 ◽  
Vol 17 (2) ◽  
pp. 156 ◽  
Author(s):  
M. Colazo ◽  
M. Rutledge ◽  
J. Small ◽  
J. Kastelic ◽  
L. Siqueira ◽  
...  
Keyword(s):  
Factorial Design ◽  
Pregnancy Rate ◽  
Animal Health ◽  
Beef Cows ◽  
Preovulatory Follicle ◽  
Dominant Follicle ◽  
Treatment Control ◽  
Lactating Cows ◽  
Follicle Size ◽  
To Receive

The objectives were to investigate the effects of pretreatment with a used CIDR on follicle size and ovulation rate in cows after an injection of GnRH, and treatment with eCG at the time of PGF on preovulatory follicle size and fertility in cows subjected to a Cosynch protocol. Lactating crossbred beef cows (n = 292), 2 to 12 years of age were allocated to two groups to receive either a used CIDR (Bioniche Animal Health; Belleville, Ontario, Canada) for 15 days or no treatment (Control). At CIDR removal (Day 0), all cows received 100 μg of GnRH i.m. (Cystorelin, Merial Canada Inc., Victoriaville, Quebec, Canada). On Day 7, all cows received 500 μg of cloprostenol i.m. (PGF; Estrumate, Schering-Plough Animal Health, Pointe-Claire, Quebec, Canada) and were further allocated to receive either 400 IU of eCG i.m. (Pregnacol; Bioniche Animal Health) or no treatment (2 × 2 factorial design; n = 73 per group). On Day 9 (54 h after PGF), cows were given 100 μg of GnRH i.m., concurrent with timed AI (TAI). Transrectal ultrasonographic examinations were done on a subset of approximately 40 cows in each group on Days −15, 0, 7, and 9 to assess ovarian structures, and on all cows on Day 37 to confirm pregnancy. Data were analyzed by SAS CATMOD and ANOVA. Overall, 53% of cows had a CL present on Day −15 (P = 0.23). At first GnRH (Day 0), fewer CIDR-treated cows than Control cows had a CL (15.2 vs. 85.0%, respectively; P < 0.001), while mean (± SEM) diameters of the dominant follicle were larger in CIDR-treated cows (18.2 ± 0.4 vs. 13.8 ± 0.4 mm, respectively; P < 0.001). Moreover, the proportion of cows that ovulated following the first GnRH was higher (P < 0.001) in CIDR-treated (75.0%) than Control (48.7%) cows. Eight (10.0%) cows presynchronized with a CIDR did not ovulate and had a luteinized follicle (31.7 ± 1.9 mm) at the time of PGF. Although CIDR-treated cows had larger (P < 0.002) dominant follicles than Control cows on Day 9 (16.6 ± 0.3 vs. 15.2 ± 0.3 mm), presynchronization did not affect fertility (53.4 vs. 54.1%, respectively). However, diameter of the dominant follicle at TAI in cows that became pregnant was smaller in CIDR-treated vs. Control cows (15.3 ± 0.3 vs. 16.6 ± 0.3; P < 0.005). Treatment with eCG on Day 7 did not affect (P = 0.17) the diameter of the dominant follicle at TAI, but tended (P = 0.06) to increase pregnancy rate (58.9 vs. 48.6%). Furthermore, pregnancy rate tended to be higher (P = 0.08) in Control cows given eCG (47/73, 64.4%) than in the Control- (32/73, 43.8%), CIDR- (39/73, 53.4%) or CIDR/eCG- (39/73, 53.4%) treated cows. In addition, pregnancy rate was affected by parity; 2-yr-old cows had a lower (P < 0.04) pregnancy rate than older cows (42.9, 58.7, and 58.2% for 2, 3–4, and >5 years, respectively). Treatment with eCG increased pregnancy rate by 33% (P < 0.03) in 2-yr-old Control cows. In summary, presynchronization with a used CIDR prior to a Cosynch protocol increased the proportion of cows responding to the first GnRH. Although CIDR-treated cows had a smaller dominant follicle at TAI, pregnancy rate was not affected. Treatment with eCG increased fertility in Control cows; eCG may be useful in GnRH-based protocols in lactating beef cows.

Origin of the preovulatory follicle after induced luteolysis during the early luteal phase in ewes

1998 ◽  
Vol 78 (3) ◽  
pp. 429-431 ◽  
Author(s):  
Carolina Viñoles ◽  
Edgardo Rubianes
Keyword(s):  
Key Words ◽  
Luteal Phase ◽  
Preovulatory Follicle ◽  
Plateau Phase ◽  
Dominant Follicle ◽  
Follicular Waves

The origin of the preovulatory follicle (POF) was determined by daily transrectal ultra-sonographic examinations in ewes given PGF2α on day 5 (n = 8) or day 9 (n = 8) post-ovulation. In all day-9 ewes, the POF originated from wave 2 while in the day-5 group it originated from wave 1 (n = 5) or wave 2 (n = 3). When the POF originated from wave 2 in day-5 ewes, the dominant follicle of wave 1 emerged earlier than in ewes with the POF from wave 1 (day –1.0 vs. day 0.8, P < 0.05) and was regressing at the time of PGF2α treatment (diameter 4.1 ± 0.4 vs. 2.8 ± 0.3 mm, P < 0.05). The dominant follicle of wave 1 became POF if it was in the growing or plateau phase at the time of luteolysis. If it was already in the regressing phase, the dominant follicle of wave 2 became the POF. Key words: PGF2α, luteolysis, ovarian follicular waves, ultrasonography, ewes

scholarly journals TGF-β superfamily members and ovarian follicle development

Reproduction ◽  
2006 ◽  
Vol 132 (2) ◽  
pp. 191-206 ◽  
Author(s):  
Phil G Knight ◽  
Claire Glister
Keyword(s):  
Granulosa Cell ◽  
Transforming Growth Factor ◽  
Ovarian Follicle ◽  
Developmental Competence ◽  
Medium Size ◽  
Follicle Development ◽  
Dominant Follicle ◽  
Primary Stage ◽  
Antral Follicles ◽  
Theca Cells

In recent years, exciting progress has been made towards unravelling the complex intraovarian control mechanisms that, in concert with systemic signals, coordinate the recruitment, selection and growth of follicles from the primordial stage through to ovulation and corpus luteum formation. A plethora of growth factors, many belonging to the transforming growth factor-β (TGF-β ) superfamily, are expressed by ovarian somatic cells and oocytes in a developmental, stage-related manner and function as intraovarian regulators of folliculogenesis. Two such factors, bone morphogenetic proteins, BMP-4 and BMP-7, are expressed by ovarian stromal cells and/or theca cells and have recently been implicated as positive regulators of the primordial-to-primary follicle transition. In contrast, evidence indicates a negative role for anti-Mullerian hormone (AMH, also known as Mullerian-inhibiting substance) of pre-granulosa/granulosa cell origin in this key event and subsequent progression to the antral stage. Two other TGF-β superfamily members, growth and differentiation factor-9 (GDF-9) and BMP-15 (also known as GDF-9B) are expressed in an oocyte-specific manner from a very early stage and play key roles in promoting follicle growth beyond the primary stage; mice with null mutations in the gdf-9 gene or ewes with inactivating mutations in gdf-9 or bmp-15 genes are infertile with follicle development arrested at the primary stage. Studies on later stages of follicle development indicate positive roles for granulosa cell-derived activin, BMP-2, -5 and -6, theca cell-derived BMP-2, -4 and -7 and oocyte-derived BMP-6 in promoting granulosa cell proliferation, follicle survival and prevention of premature luteinization and/or atresia. Concomitantly, activin, TGF-β and several BMPs may exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small to medium-size antral follicles. Dominant follicle selection in monovular species may depend on differential FSH sensitivity amongst a growing cohort of small antral follicles. Changes in intrafollicular activins, GDF-9, AMH and several BMPs may contribute to this selection process by modulating both FSH- and IGF-dependent signalling pathways in granulosa cells. Activin may also play a positive role in oocyte maturation and acquisition of developmental competence. In addition to its endocrine role to suppress FSH secretion, increased output of inhibin by the selected dominant follicle(s) may upregulate LH-induced androgen secretion that is required to sustain a high level of oestradiol secretion during the pre-ovulatory phase. Advances in our understanding of intraovarian regulatory mechanisms should facilitate the development of new approaches for monitoring and manipulating ovarian function and improving fertility in domesticated livestock, endangered species and man.

scholarly journals Comparison of mRNA for IGFs and their binding proteins in the oviduct during the peri-oestrous period between dairy heifers and lactating cows

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 457-465 ◽  
Author(s):  
Theerawat Swangchan-Uthai ◽  
Siobhan W Walsh ◽  
Sarah L H Alexander ◽  
Zhangrui Cheng ◽  
Mark A Crowe ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Early Embryo ◽  
Dominant Follicle ◽  
Embryo Survival ◽  
Lh Surge ◽  
Dairy Heifers ◽  
Lactating Cows ◽  
Holstein Friesian ◽  
Igf Binding ◽  
Igf Binding Protein

The oviduct provides the environment to support gamete maturation, fertilisation and early embryo development. As there is a high incidence of early embryonic death in lactating dairy cows, this study compared expression of IGF family members in the oviduct between lactating Holstein-Friesian dairy cows (n=16, 81±2.4 days in milk) and nulliparous heifers (n=16, age 1.6±0.07 years) at three stages of the oestrous cycle: A) newly selected dominant follicle in the luteal phase, B) follicular phase before the LH surge and C) pre-ovulatory phase after the LH surge. Expression ofIGF1,IGF2, IGF binding protein 2 (IGFBP2),IGFBP3andIGFBP6mRNA was determined in the ampulla of the oviduct. Oviduct side (ipsilateral or contralateral) with respect to the dominant follicle did not affect gene expression. Expression ofIGF1and all threeIGFBPsincreased significantly between the luteal and the pre-ovulatory phases, with no further significant alteration post-LH surge. Concentrations of circulating IGF1 were higher in heifers than in cows, as was the mRNA expression ofIGF1,IGFBP3andIGFBP6. The pre-LH surge rise inIGFBP2mRNA was only observed in heifers.IGF2expression was not influenced by either age or stage of cycle. These three IGFBPs are generally considered to inhibit IGF action. These results indicate tight regulation of IGF bioavailability in the oviductal environment around oestrus, with pronounced differences between cows and heifers, which are likely to influence early embryonic development. Further studies are required to assess the implications for embryo survival.

scholarly journals Echographic Evidence of Follicle Development and Maturation

2011 ◽  
Vol 5 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Veljko Vlaisavljevic
Keyword(s):  
Luteal Phase ◽  
Clinical Success ◽  
Follicular Phase ◽  
Growth Patterns ◽  
Follicle Development ◽  
Pulsed Doppler ◽  
Dominant Follicle ◽  
Follicle Growth ◽  
Non Invasive ◽  
Late Follicular Phase

ABSTRACT Monitoring of individual follicles during the menstrual cycle demonstrates in a non-invasive way the changes in their number and position during the early and the late follicular phase and the luteal phase. The differences in relations between the follicles near the dominant follicle can be demonstrated with the same technique using 3D reconstruction of the ovary. Recognition of the follicle growth pattern has a prognostic value for the outcome of assisted reproduction methods. Follicular diameter and changes in growth patterns are more important than follicular wall thickness as parameters having an impact on clinical success. An increased perifollicular blood flow can be measured in the perifollicular period using color and pulsed Doppler. Automated estimation of blood volume around the ovarian follicles brought a new concept to this area. Results confirm the observation that vascularity around the follicle is intense in the periovulatory period. From our results we can hypothesize that those follicles containing oocytes able to produce pregnancy have a prominent and more uniform perifollicular vascular network .

scholarly journals Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women

2017 ◽  
Vol 103 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Karolina Skorupskaite ◽  
Jyothis T George ◽  
Johannes D Veldhuis ◽  
Richard A Anderson
Keyword(s):  
Ovarian Follicle ◽  
Follicle Development ◽  
Follicle Growth ◽  
Duration Of Treatment ◽  
Neurokinin B ◽  
Gonadotropin Secretion ◽  
Lh Surge ◽  
Healthy Women ◽  
Follicle Diameter ◽  
Lh Secretion

Abstract Context Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown. Objective To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion and ovarian follicle development in healthy women. Design Open investigation of the effects of a neurokinin-3 receptor (NK3R) antagonist (NK3Ra) vs a no-treatment control cycle. Setting Clinical research facility. Patients or other participants Healthy women with regular menses (n = 13). Intervention(s) NK3Ra MLE4901 40 mg taken orally twice daily from cycle day 5 to 6 for 7 days. Main outcome measure(s) LH secretion, ovarian follicle growth, and timing of ovulation. Results NK3Ra administration reduced basal LH secretion without a change in pulse frequency and delayed the LH surge by 7 days, the duration of treatment [mean cycle day ± standard error of the mean (SEM), 22 ± 1 days vs 15 ± 1 days in control cycles; P = 0.0006]. Follicle growth (mean diameter at the end of administration of NK3Ra administration ± SEM, 9.3 ± 0.4 mm vs 15.1 ± 0.9 mm in control cycles; P &lt; 0.0001) and rising estradiol concentrations (mean ± SEM, 166 ± 29 pmol/L vs 446 ± 86 pmol/L in control cycles; P &lt; 0.0001) were prevented. After treatment, follicle development resumed and normal preovulatory follicle diameter and estradiol concentrations were demonstrated. Postovulatory progesterone rise was similarly delayed (peak cycle day, 30 ± 2 vs 22 ± 1; P = 0.002) and cycle length was prolonged (35 ± 1 days vs 29 ± 1 days in control cycles; P = 0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge day +7 mean urinary progesterone levels ± SEM, 58 ± 10 pmol/mol vs 48±7 pmol/mol creatinine in control cycles; nonsignificant). Conclusion These data demonstrate the involvement of NKB-NK3R signaling in the physiological regulation of GnRH/LH secretion, determining normal follicle development in women.

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