TRH stimulates LH release in adolescents with delayed puberty

ABSTRACTThe tachykinin neurokinin B (NKB, Tac2) is critical for GnRH release. NKB signaling deficiency leads to infertility in humans. However, some patients reverse this hypogonadism resembling the fertile phenotype of Tac2KO and Tacr3KO (encoding NKB receptor, NK3R) mice despite the absence of NKB signaling. Here, we demonstrate that in the absence of NKB signaling, other tachykinins (substance P and neurokinin A [NKA], encoded by Tac1) may take over to preserve fertility. The complete absence of tachykinins in Tac1/Tac2KO mice leads to delayed puberty onset in both sexes and infertility in 80% of females (but not males), in contrast to the 100% fertile phenotype of Tac1KO and Tac2KO mice separately. Furthermore, we demonstrate that NKA controls puberty onset and LH release through NKB-independent mechanisms in the presence of sex steroids and NKB-dependent mechanisms in their absence. In summary, tachykinins interact in a coordinated manner to ensure reproductive success in female mice.

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PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse

10.1101/274860 ◽

2018 ◽

Cited By ~ 2

Author(s):

Rachel A. Ross ◽

Silvia León ◽

Joseph C. Madara ◽

Danielle Schafer ◽

Chrysanthi Fergani ◽

...

Keyword(s):

Reproductive Function ◽

Delayed Puberty ◽

Targeted Deletion ◽

Pituitary Adenylate Cyclase ◽

Genetic Cross ◽

Gnrh Release ◽

Lh Release ◽

Puberty Onset ◽

Disclosure Statement ◽

Hypothalamic Level

AbstractPituitary adenylate cyclase activating polypeptide (PACAP) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We demonstrate that PACAP-expressing neurons of the ventral premamillary nucleus of the hypothalamus (PMVPACAP) project to, and make direct contact with, kisspeptin neurons in the arcuate and AVPV/PeN nuclei and a subset of these neurons respond to PACAP exposure. Targeted deletion of PACAP from the PMV through stereotaxic virally mediated cre- injection or genetic cross to LepR-i-cre mice with PACAPfl/flmice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new, sex-specific role for PACAP-expressing neurons in the PMV in the relay of nutritional state information to regulate GnRH release by modulating the activity of kisspeptin neurons, thereby regulating reproduction.Disclosure statementThe authors have nothing to disclose.

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PACAP neurons in the ventral premammillary nucleus regulate reproductive function in the female mouse

eLife ◽

10.7554/elife.35960 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 19

Author(s):

Rachel A Ross ◽

Silvia Leon ◽

Joseph C Madara ◽

Danielle Schafer ◽

Chrysanthi Fergani ◽

...

Keyword(s):

Reproductive Function ◽

Delayed Puberty ◽

State Information ◽

Targeted Deletion ◽

Pituitary Adenylate Cyclase ◽

Genetic Cross ◽

Gnrh Release ◽

Lh Release ◽

Puberty Onset ◽

Hypothalamic Level

Pituitary adenylate cyclase activating polypeptide (PACAP, Adcyap1) is a neuromodulator implicated in anxiety, metabolism and reproductive behavior. PACAP global knockout mice have decreased fertility and PACAP modulates LH release. However, its source and role at the hypothalamic level remain unknown. We demonstrate that PACAP-expressing neurons of the ventral premamillary nucleus of the hypothalamus (PMVPACAP) project to, and make direct contact with, kisspeptin neurons in the arcuate and AVPV/PeN nuclei and a subset of these neurons respond to PACAP exposure. Targeted deletion of PACAP from the PMV through stereotaxic virally mediated cre- injection or genetic cross to LepR-i-cre mice with Adcyap1fl/fl mice led to delayed puberty onset and impaired reproductive function in female, but not male, mice. We propose a new role for PACAP-expressing neurons in the PMV in the relay of nutritional state information to regulate GnRH release by modulating the activity of kisspeptin neurons, thereby regulating reproduction in female mice.

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THE HCG-TEST IN BOYS WITH DELAYED PUBERTY AND WITH TESTICULAR DAMAGE

Acta Endocrinologica ◽

10.1530/acta.0.049s011 ◽

1965 ◽

Vol 49 (4_Suppl) ◽

pp. S11

Author(s):

C. G. Bergstrand

Keyword(s):

Delayed Puberty ◽

Testicular Damage ◽

Hcg Test

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Androgenic and oestrogenic steroid participation in feedback control of luteinizing hormone secretion in male sheep

Acta Endocrinologica ◽

10.1530/acta.0.1020499 ◽

1983 ◽

Vol 102 (4) ◽

pp. 499-504 ◽

Cited By ~ 15

Author(s):

M. J. D'Occhio ◽

B. D. Schanbacher ◽

J. E. Kinder

Keyword(s):

Luteinizing Hormone ◽

Pulse Generator ◽

Hormone Secretion ◽

Pulse Interval ◽

Serum Concentrations ◽

Luteinizing Hormone Secretion ◽

Lh Release ◽

Lh Secretion ◽

Additional Feedback ◽

Male Sheep

Abstract. The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40–60 min) and had elevated LH levels (16.1 ± 1.6 ng/ml; mean ± se) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH. Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.

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