Changes in the granule population of gonadotrophs of hypogonadal (hpg) and normal female mice associated with the priming effect of LH-releasing hormone in vitro

Associations between granins (secretogranin II (SgII) and chromogranin A and B (CgA and CgB)) and gonadotrophins (LH and FSH) have been reported in rodents and they may interact to facilitate differential storage and secretion of LH and FSH. This study investigated the relationship between granins and gonadotrophins in sheep at different stages of the oestrous cycle. Thirty-four cycling ewes had their oestrous cycles synchronised, and were divided into late luteal (LL; n=5) and early (EF; n=4), mid (n=3) and late (LF; n=11) follicular stages, and 24-53 h (n=5), 80-100 h (n=3) and 120-144 h (n=3) after the preovulatory LH surge (PS). LH mRNA levels were low in LF ewes (when plasma levels and pulse frequency of LH were high) but had increased by 80-100 h PS. In contrast, FSH mRNA levels decreased during the follicular phase and plasma FSH concentrations followed a similar pattern, to peak at 24-53 h PS due to low plasma oestradiol levels. While -gonadotrophin subunit ( -GSU), SgII and CgA mRNA levels did not change, CgB mRNA levels were elevated in EF ewes and had declined in ewes around the surge. Four distinctly sized mRNA transcripts (1·3, 2·0, 2·8 and 3·2 kb) were observed for CgA mRNA, while a double band was observed for LH mRNA that was subsequently reduced to a single band after 3 -poly(A) tail truncation. The long and short LH transcripts were prevalent in follicular and luteal ewes respectively. Numbers of LH +ve /FSH -ve granules stored within gonadotrophs were not different in LL and LF ewes (even though proportions of LH +ve granules were higher in LF ewes), but were reduced at 24-53 h PS. The majority of LH +ve granules also contained SgII, although few CgA +ve granules were found. Granule partitioning was evident whereby FSH and CgA were located near the periphery, and LH and SgII throughout the matrix. In conclusion, increases in both storage of LH +ve granules and secretion of LH in LF ewes despite constant LH mRNA levels was facilitated, at least in part, by improved LH mRNA transcript stability. Fewer LH +ve /FSH -ve granules were in storage after the PS, which was mirrored by a reduction in LH pulsatile release. Surprisingly, in view of results in rodents indicating significant changes, SgII and CgA mRNA levels did not change over the oestrous cycle in sheep. Conversely, CgB mRNA levels decreased around the time of PS. These novel results illustrate major differences in granin-gonadotrophin interactions between sheep and rodents.

mentioning

confidence: 43%

Co-localisation of gonadotrophins and granins in gonadotrophs at different stages of the oestrous cycle in sheep

Crawford

McNeilly²

2002

“…In oestrogen-primed rats, the secretion of luteinising hormone (LH) in response to gonadotrophin-releasing hormone (GnRH) increases with successive exposures to GnRH, a phenomenon that Fink (1995) called 'self-priming'. With Morris and others, Fink showed that between exposures to GnRH, there is a 'margination' of secretory granules in gonadotrophs: how much LH is secreted in response to GnRH depends on how many granules lie close to the plasma membraneand GnRH could trigger the relocation of granules to these sites (Lewis et al 1986). This depends on the mobilisation by GnRH of intracellular calcium stores, so Leng and Ludwig, knowing that the release of neurosecretory granules in response to electrical activity was likely to depend on those granules being close to the site of depolarisation-induced calcium entry, wondered if something similar was happening in the dendrites of magnocellular neurons.…”

Section: The Milk-ejection Reflexmentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: The posterior pituitary, from Geoffrey Harris to our present understanding

Leng¹,

Pineda²,

Sabatier³

et al. 2015

Geoffrey Harris pioneered our understanding of the posterior pituitary, mainly with experiments that involved the electrical stimulation of the supraoptico-hypophysial tract. In the present essay, we explain how his observations included clues to the pulsatile nature of the oxytocin signal -clues that were followed up by subsequent workers, including his students and their students. These studies ultimately led to our present understanding of the milk-ejection reflex and of the role of oxytocin in parturition. Discoveries of wide significance followed, including: the recognition of the importance of pulsatile hormone secretion; the recognition of the importance of stimulus-secretion coupling mechanisms in interpreting the patterned electrical activity of neurons; the physiological importance of peptide release in the brain; the recognition that peptide release comes substantially from dendrites and can be regulated independently of nerve terminal secretion; and the importance of dynamic morphological changes to neuronal function in the hypothalamus. All of these discoveries followed from the drive to understand the milk-ejection reflex. We also reflect on Harris's observations on vasopressin secretion, on the effects of stress, and on oxytocin secretion during sexual activity.

“…The history of neuroendocrinology has been the subject of several reviews (Harris 1955, Guillemin 1967, 1978, 2011, Harris 1972, 1986, 1988, Charlton 2008. Friedgood (1936) and Hinsey (1937) were arguably the first to postulate formally that the anterior pituitary gland was controlled by substances liberated into the hypophysial portal vessels from nerve terminals in the median eminence.…”

Section: Brief Historymentioning

confidence: 99%

“…Ultrastructural studies have shown that GnRH selfpriming involves an increase in length and a change in the angle of the microfilaments in gonadotrophs as well as a migration of secretory granules towards the plasmalemma of the gonadotroph (Lewis et al 1985(Lewis et al , 1986Fig. 6).…”

Section: Mechanisms Involved In Gnrh Self-primingmentioning

confidence: 99%

See 1 more Smart Citation

60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: Harris' neuroendocrine revolution: of portal vessels and self-priming

Fink¹

2015

Geoffrey Harris, while still a medical student at Cambridge, was the first researcher (1937) to provide experimental proof for the then tentative view that the anterior pituitary gland was controlled by the CNS. The elegant studies carried out by Harris in the 1940s and early 1950s, alone and in collaboration with John Green and Dora Jacobsohn, established that this control was mediated by a neurohumoral mechanism that involved the transport by hypophysial portal vessel blood of chemical substances from the hypothalamus to the anterior pituitary gland. The neurohumoral control of anterior pituitary secretion was proved by the isolation and characterisation of the 'chemical substances' (mainly neuropeptides) and the finding that these substances were released into hypophysial portal blood in a manner consistent with their physiological functions. The new discipline of neuroendocrinology -the way that the brain controls endocrine glands and vice versa -revolutionised the treatment of endocrine disorders such as growth and pubertal abnormalities, infertility and hormone-dependent tumours, and it underpins our understanding of the sexual differentiation of the brain and key aspects of behaviour and mental disorder. Neuroendocrine principles are illustrated in this Thematic Review by way of Harris' major interest: hypothalamic-pituitary-gonadal control. Attention is focussed on the measurement of GnRH in hypophysial portal blood and the role played by the self-priming effect of GnRH in promoting the onset of puberty and enabling the oestrogen-induced surge or pulses of GnRH to trigger the ovulatory gonadotrophin surge in humans and other spontaneously ovulating mammals.