Pituitary Immediate Release Pools of Growth Hormone and Prolactin Are Preferentially Refilled by New Rather than Stored Hormone*

Abstract

Pituitary stores of rat GH (rGH) and PRL (rPRL) are divisible into immediately releasable and more stable compartments representing either compartmentalized hormone within individual cells of a homogeneous population or responses of specialized cell subsets in a functionally heterogeneous population. In addition, newly synthesized rGH and rPRL can be processed either into intracellular storage or toward direct release. Fractional assignment of new hormone to these two paths can be influenced in the somatotroph by GHRH and may also represent either intracellular processes or functional heterogeneity of cells. We investigated the source, newly synthesized or stored, of hormone refilling the somatotroph and lactotroph immediately releasable pools (IRP) after their discharge by 21 mM potassium ion, 1 mM (Bu)2cAMP, 3 nM human GHRH-44, or 3 microM prostaglandin E1. Experiments were performed using perifused pituitary fragments exposed sequentially to [14C]- and [3H]leucine in association with stimulation by two 30-min pulses of the same secretagogue. Therefore, only [14C]hormone was available for release by the first stimulus, whereas both [14C]- and [3H]hormone were available for release by the second stimulus. Analysis was by specific immunoprecipitation. The first episode of stored [14C]rGH release exceeded the second episode of stored [14C]rGH release in response to each secretagogue. However, release of newly synthesized [3H]rGH in response to the second episode of stimulation exceeded the simultaneous release of stored [14C]rGH while matching or exceeding the [14C]rGH release that had occurred in the same experiment in response to the first episode of stimulation. Refilling both GH and PRL IRP stores drew primarily upon newly synthesized hormone, but with different secretagogue-specific patterns. These data confirm differential handling of new and stored rGH and rPRL within the pituitary. They are consistent with either (1) the enhanced shunting of newly synthesized hormone to IRPs within cells that are capable of compartmentalized intracellular hormone storage, or (2) the relatively complete discharge of a subset of somatotrophs and lactotrophs that are specialized to deliver pulsed hormone release, after which they are refilled by newly synthesized hormone.

Dynamics of in Vivo Release of Molt-Inhibiting Hormone and Crustacean Hyperglycemic Hormone in the Shore Crab, Carcinus maenas

“…However, sustained patterns of release would undoubtedly be untenable; rapid depletion of SG peptide would occur. Turnover rates of SG peptides are probably in the order of months (28), and there is firm evidence that in crustaceans (29,30), as in other organisms (31)(32)(33), that immediate release pools of neuropeptides preferentially contain freshly synthesized rather than aged hormone. Thus, episodic rather than sustained release of CHH and MIH seems likely.…”

Moult cycle‐related changes in biological activity of moult‐inhibiting hormone (MIH) and crustacean hyperglycaemic hormone (CHH) in the crab, Carcinus maenas

“…It is now well established that the release of peptides from neurosecretory neurones is preferentially restricted to newly synthesized products from neurosecretory terminals, for example in locusts [22,23], molluscs [24], mammals [25], crabs [26] and shrimps [27]. Thus, any changes in transcription, not withstanding translational control mechanisms, might indicate periods within the moult cycle when peptides are released, as available evidence suggests that aged peptides are not released.…”

Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study

“…The latter is less likely since we did not observe the characteristic increases in ampli¬ tude as well as frequency documented in adult volunteers (Vance et al 1985) treated with continuous GHRH therapy. SS tone maintains the baseline of GH secretion and influences the amount and rate (Spoudeas et al 1992) of GH released from a depletable pituitary pool (Stachura et al 1989). Thus the normal baseline GH levels and rates of GH change in children before radiotherapy are against a pituitary GH 'leak' due to SS deficiency at this time, although there is some suggestion that this phenomenon may develop later as a consequence of irradiation.…”

“…Although these data require confirmation in larger patient numbers, we suggest that alkylating agents and antimetabolites cross the disrupted blood-brain barrier in children with cranial malignancy, and are important additional factors influencing the GH axis centrally. The higher basal levels coupled with lower spontaneous peaks and rates of GH change in both radiotherapy groups suggest failure to maintain GH within a depletable pituitary pool and would be compatible with an element of SS deficiency (Stachura et al 1989, Spoudeas et al 1992). …”