In an embodiment, the GnRH analogue and the hormone moiety are directly conjugated. Typically in this case an amino acid would be synthesised with the hormone moiety already attached, and this modified amino acid would be incorporated into a peptide GnRH analogue. For example, direct conjugation may arise through imine formation between the keto group on the hormone and the ε-amino group on Lys. The resulting imine may be hydrolytically unstable in vivo, thus giving rise to a conjugate having a short half-life. The half-life may be increased by reducing the imine to give an amine. Alternatively, direct conjugation may arise through Michael addition of the ε-amino group on Lys to an α,β-unsaturated ketone functionality in the hormone moiety (eg progesterone), or through reaction of a hormone moiety in which an OH group has been converted to a leaving group (eg a halide or a sulfonate ester) with a suitable nucleophilic group on a residue of the GnRH analogue (eg the ε-amino group on Lys or the β-OH group on Ser).
Q. I read your review of creatine online and found it
very informational. I am wondering if you can share some information about the
recent body-building supplement Ecdy Bolin. I have been using it for a couple
months (both with creatine and also without). It is promoted as has other
benefits aside from muscle-building, such as nerve function. Anyway, I would
like to know if you feel this supplement is a safe and a quality addition and
how you feel about it in general. At the moment, I am not using creatine, only
A. An internet search reveals Ecdy Bolin has 100 mg of ecdysterone. I have not seen any human studies with Ecdy Bolin or ecdysterone, so I have no opinion on this supplement at this time.
AB - Properties of a pituitary gonadotrope include the capacity to regulate gonadotropin synthesis and secretion in response to a GnRH signal. Progress in identifying the steps involved in these processes has been impeded by the lack of a homogeneous in vitro model of gonadotropes. This paper presents functional characterization of a LβT2 gonadotrope cell line generated by tumorigenesis in transgenic mice carrying the rat LHβ-subunit regulatory region linked to the SV40 T-antigen oncogene. This cell line expresses LHβ, α-subunit, and GnRH-recaptor (GnRH-R) mRNAs (though not FSHβ), responds to glucocorticoid treatment with a reversible dampening of proliferation, and responds to pulsatile, concentration-dependent GnRH administration with LH secretion. LβT2 cells presented with four GnRH pulses (10 nM, 90-min interpulse interval) on each of 4 days respond with incremental increases in LH secretion on successive days. This increase was greatest (15-fold) in the presence of estradiol and dexamethasone. Part of the enhanced responsiveness is apparently due to an increase in GnRH-R; pulsatile GnRH treatment alone as well as steroid treatment alone led to an increase in GnRH-R mRNA levels. When secretion was stimulated on day 4 with 54 mM [K+] pulses, bypassing the GnRH-R, the LH-secretory response indicated that the GnRH pulse history as well as estradiol and dexamethasone have actions on LβT2-secretory capacity distinct from changes in the GnRH-R. This increase can be explained in part by the marked up-regulation of LHβ, but not α-subunit, mRNA observed in GnRH-pulsed cells. In summary, LβT2 clonal gonadotropes exhibit functional characteristics consistent with those of normal pituitary gonadotropes such as LH secretion via a regulated pathway and changes in GnRH-R and LHβ gene expression in response to signaling by GnRH and steroid hormones and therefore should be a useful tool for dissecting the cellular and molecular events involved in these fundamental gonadotrope properties.